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La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
Plaquette sanguine
Plaquette sanguine
Plaquette sanguine
platelet
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
Plaquette sanguine
Plaquette sanguine
Plaquette sanguine
platelet
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
Plaquette sanguine
Plaquette sanguine
Plaquette sanguine
platelet
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
Plaquette sanguine
Plaquette sanguine
platelet
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
Plaquette sanguine
platelet
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
1910 Megakaryocyte (Wright)
1910 Megakaryocyte (Wright)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
1910 Megakaryocyte (Wright)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
Meacutethode isotopique
LA PRODUCTION DES PLAQUETTES
EST CONTROLEE
A humoral factor controls platelet production
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Seacuterum anti-plaquettaire
Thrombocytopeacutenie
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
1968 Le Nombre la Taille et la Ploiumldie des
meacutegacaryocytes sont sous controcircle (Harker)
Transfusion de plaquettes
Thrombocytheacutemie
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
000
100
200
300
400
500
600
700
800
900
000 100 200 300 400 500 600 700 800 900 1000
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
Lineacuteaire (TOTAL)
Hamood M amp Chatelain C 1984
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
000
200
400
600
800
1000
1200
1400
000 500 1000 1500 2000 2500
Vo
lum
e M
eacutegac
aryo
cyta
ire
Mo
yen
(x1
00
0 micro
sup3)
Plaquettes (x100000microL)
Morphomeacutetrie
Normal
LMC
Tose 2aire
TOTAL
PVET
Lineacuteaire (TOTAL)
PVET
Hamood M amp Chatelain C 1984
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
HYPERPLAQUETTOSE
REACTIONNELLE vs PRIMITIVE
Effort stress adreacutenaline
Infection inflamation
Carence en fer
Cancer
Vincristine
Aspleacutenie
SMP
LMCTE
Vaquez
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
1975 CFU-MK (Metcalf)
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
Hieacuterarchie cellulaire
PSC CFU-MKMeacutegacaryocytes Plaquettes
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
PSC CFU-MKMeacutegacaryocytes Plaquettes
IL-3 GM-CSF
LITHIUM ACETYLCHOLINE
CYCLOSPORINE A
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
lt 1050
LD-CFU-MK
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
lt 1050
LD-CFU-MK
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
PSC
CFU-MK Meacutegacaryocytes Plaquettes
LD-CFU-MK
TPO
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
PSC CFU-MKMegakaryocytes Platelets
IL-3 GM-CSF
IL-6 IL-11 LIF
Oncostatin M hellip
1983 Cytokines (Metcalf Quesenberryhellip)
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
PSC CFU-MKMeacutegacaryocytes Plaquettes
THROMBOPOIETINE
1994 THROMBOPOIETINE (mpl ligand)
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
THROMBOPOIETINE
1 mpl oncogene
2 Production constante
3 Stimulates proliferation
4 Controcircle POLYPLOIDISATION
5 LD-CFU-MK
6 Reacutegulation lsquo par produit final rsquo
cad par les plaquettes
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
THROMBOPOIETINE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
APPLICATION
CLINIQUE DE LA
THROMBOPOIETINE
1 rh-TPO deacuteception
2 Dosage ITP hellip
3 Analogues TPO Nplatereg (Romiplostim)
et Revoladereg (Eltrombopag) PTI
4 Production in vitro de plaquettes
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
Platelet production in vitro
CD34 + cells
Platelets
7-14 days
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
D 14
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
D 14
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
GP-IIbIIIa
D 14
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
GP-IIIa
CD34Forward vs side
Scatter (d14)
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
Cells
0
2000000
4000000
6000000
J0 J3 J7 J10 J14
Platelets
0
200000000
400000000
600000000
800000000
1000000000
J0 J3 J7 J10 J14
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
CHRONOLOGIE1881 Identification des plaquettes (Bizzozero)
1910 Meacutegacaryocyte (Wright)
1958 Thrombopoiumleacutetine (Kelemen)
1967 Mesure de la production plaquettaire (Odell)
1968 Morphometrie des meacutegakaryocytes (Harker)
1975 CFU-MK (Metcalf)
1984 Cytokines (IL-3hellip) (Ihle Quesenberry)
1994 mpl et Thrombopoiumleacutetine
2016 rupture meacutegacaryocytaire (IL-1α)
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to
acute platelet needs
Nishimura S1 Nagasaki M2 Kunishima S3 Sawaguchi A4 Sakata A5 Sakaguchi H6
Ohmori T5 Manabe I7 Italiano JE Jr8 Ryu T9 Takayama N10 Komuro I2
Kadowaki T2 Eto K11 Nagai R5
J Cell Biol 2015 May 11209(3)453-66
RUPTURE MEGACARYOCYTAIRE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
En guise de conclusion
DIAGNOSTIC Drsquo
HYPERPLAQUETTOSE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
La production
des
plaquettes sanguines
Jeudis de Fleurus 2016
Prof Christian CHATELAIN
NTHC
Universiteacute de Namur
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
POLYPLOIDISATION
MECHANISM
Role of cytoskeletton
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
HYDROXYUREA DECREASES
PROLIFERATION
ANAGRELIDE DECREASES
POLYPLOIDIZATION
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
PSC CFU-MKMegakaryocytes Platelets
HUDROXYUREA
ANAGRELIDE
THERAPY OF ET
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
TREATMENT OF
ESSENTIAL
THROMBOCYTHEMIA
Do not forget HYPERURICEMIA
(Allopurinol)
What about PLATELET FUNCTIONS
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
Pathogeny and treatment of
THROMBOCYTHEMIA
UNDERSTANDING
MEGAKARYOCYTOPOIESIS
2004
Prof Christian CHATELAIN
UCL MONT-GODINNE
