Gene expression profiling in peripheral

T-cell lymphoma

Wing C Chan

City of Hope Medical Center

Wing C Chan

City of Hope National Medical Center

University of Nebraska Medical Center

Rationale for GEP studies on PTCL

The diagnosis of PTCL is challenging even among

expert hematopathologists compounded by the rarity

and diversity of PTCLs

May have a prominent reactive cellular infiltrate

masking the neoplastic cell population

No unique cytogenetic abnormality in the major PTCL

subtypes

Approximately 50 of the cases are categorized as

PTCL not otherwise specified (PTCL-NOS)

Gain better understanding of the biology of PTCL

including clinically significant pathways

International T-Cell Lymphoma Project J Clin Oncol 264124-4130 2008

Frequency of common subtypes of PTCL

not other specified

PTCL-NOS

AITLALCL

ATLL

ENKTCL

SPECS Strategic Partnering to Evaluate Cancer SignaturesiPTCL International peripheral T-cell lymphomaLLMPP Lymphoma and Leukemia Molecular Profiling ProjectSingapore

PTCL subtype and ENKTL cases with acceptable GEP

Lymphoma subtypes

o

f c

as

es

n=372 cases

PTCL- subtypes

Gene expression profiling data was generated on HG U133 plus 2 arrays ( Affymetrix Inc)

Refinement of molecular diagnostic signatures for PTCL subgroups

Relative Level of Expression (x median value)

Unique molecular signatures were identified for major PTCL entities

Relative Level of Expression (x median value)

AITL ALK- NKALK+

ALCL

TATTL

ENKTL

PTCL-NOS

Blood 2014 May 8123(19)2915-23Lymphoma and Leukemia Molecular Profiling Project (LLMPP) initiative

-of 152 PTCL-NOS cases a subset of cases were classified into

i AITL [14]

ii ALK(-)ALCL [11]

iii ATLL [03]

iv - PTCL [09]

- Of 117 AITL cases 26 cases (22) changed to PTCL-NOS

Evaluation of pathological vs molecular diagnosis

Blood 2014 May 8123(19)2915-23

ALK(+) ALCL

mdash MYC induced gene signaturemdash Proliferation signaturemdash NF-B target signature

mdash IL10 induced signaturemdash STAT3 signaturemdash Treg gene signaturemdash Presence of B cellsmdash HIF-alpha induced gene signature

ALK(-)ALCL

ALK(-)ALCL

mdash Proliferation signature mdash MYC induced gene signaturemdash IRF4 induced gene signaturemdash Absence of TCR signaling molecules

Gene set enrichment analysis

Gene signaturepathway enrichment summary in ALK(-)ALCL

ALK(-) ALCL is molecularly distinct from PTCL-NOS and ALK(+)ALCL

Re-classified from PTCL-NOS

ALKALK

ALK(+) ALCL ALK(-) ALCL PTCL-NOS

Blood 2014 May 8123(19)2915-23

Robust molecular signature for ALK(-)ALCL

Parilla Castellar et al Blood 2014August 28 124(9)1473-1480

DUSP22 and TP63 rearrangements in ALK- ALCL

NFkB2 GSP5

NFkB2 GSP54

NCOR2 GSP99

PABPC4 GSP50

ROS1

TYK2

ROS1

TYK2

Novel fusions combining a transcription factor

(NFkB2 or NCOR2) with a tyrosine kinase (ROS1

or TYK2)

Crescenzo and Abate etal Cancer Cell 2015

JAKSTAT3 pathway activation through

mutations and fusion transcripts

JAK1 and STAT3 mutations

₋ AITL₋ ATLL₋ ALK(-)ALCL₋ ALK(+)ALCL₋ NKCL₋ -PTCL

n=251 n=121

32 PTCL-NOS

WHO recognized TNK tumor subtypes

One-third of PTCL-NOS cases were not molecularly classified into WHO recognized PTCL entities

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

University of Nebraska Medical Center

Rationale for GEP studies on PTCL

The diagnosis of PTCL is challenging even among

expert hematopathologists compounded by the rarity

and diversity of PTCLs

May have a prominent reactive cellular infiltrate

masking the neoplastic cell population

No unique cytogenetic abnormality in the major PTCL

subtypes

Approximately 50 of the cases are categorized as

PTCL not otherwise specified (PTCL-NOS)

Gain better understanding of the biology of PTCL

including clinically significant pathways

International T-Cell Lymphoma Project J Clin Oncol 264124-4130 2008

Frequency of common subtypes of PTCL

not other specified

PTCL-NOS

AITLALCL

ATLL

ENKTCL

SPECS Strategic Partnering to Evaluate Cancer SignaturesiPTCL International peripheral T-cell lymphomaLLMPP Lymphoma and Leukemia Molecular Profiling ProjectSingapore

PTCL subtype and ENKTL cases with acceptable GEP

Lymphoma subtypes

o

f c

as

es

n=372 cases

PTCL- subtypes

Gene expression profiling data was generated on HG U133 plus 2 arrays ( Affymetrix Inc)

Refinement of molecular diagnostic signatures for PTCL subgroups

Relative Level of Expression (x median value)

Unique molecular signatures were identified for major PTCL entities

Relative Level of Expression (x median value)

AITL ALK- NKALK+

ALCL

TATTL

ENKTL

PTCL-NOS

Blood 2014 May 8123(19)2915-23Lymphoma and Leukemia Molecular Profiling Project (LLMPP) initiative

-of 152 PTCL-NOS cases a subset of cases were classified into

i AITL [14]

ii ALK(-)ALCL [11]

iii ATLL [03]

iv - PTCL [09]

- Of 117 AITL cases 26 cases (22) changed to PTCL-NOS

Evaluation of pathological vs molecular diagnosis

Blood 2014 May 8123(19)2915-23

ALK(+) ALCL

mdash MYC induced gene signaturemdash Proliferation signaturemdash NF-B target signature

mdash IL10 induced signaturemdash STAT3 signaturemdash Treg gene signaturemdash Presence of B cellsmdash HIF-alpha induced gene signature

ALK(-)ALCL

ALK(-)ALCL

mdash Proliferation signature mdash MYC induced gene signaturemdash IRF4 induced gene signaturemdash Absence of TCR signaling molecules

Gene set enrichment analysis

Gene signaturepathway enrichment summary in ALK(-)ALCL

ALK(-) ALCL is molecularly distinct from PTCL-NOS and ALK(+)ALCL

Re-classified from PTCL-NOS

ALKALK

ALK(+) ALCL ALK(-) ALCL PTCL-NOS

Blood 2014 May 8123(19)2915-23

Robust molecular signature for ALK(-)ALCL

Parilla Castellar et al Blood 2014August 28 124(9)1473-1480

DUSP22 and TP63 rearrangements in ALK- ALCL

NFkB2 GSP5

NFkB2 GSP54

NCOR2 GSP99

PABPC4 GSP50

ROS1

TYK2

ROS1

TYK2

Novel fusions combining a transcription factor

(NFkB2 or NCOR2) with a tyrosine kinase (ROS1

or TYK2)

Crescenzo and Abate etal Cancer Cell 2015

JAKSTAT3 pathway activation through

mutations and fusion transcripts

JAK1 and STAT3 mutations

₋ AITL₋ ATLL₋ ALK(-)ALCL₋ ALK(+)ALCL₋ NKCL₋ -PTCL

n=251 n=121

32 PTCL-NOS

WHO recognized TNK tumor subtypes

One-third of PTCL-NOS cases were not molecularly classified into WHO recognized PTCL entities

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

International T-Cell Lymphoma Project J Clin Oncol 264124-4130 2008

Frequency of common subtypes of PTCL

not other specified

PTCL-NOS

AITLALCL

ATLL

ENKTCL

SPECS Strategic Partnering to Evaluate Cancer SignaturesiPTCL International peripheral T-cell lymphomaLLMPP Lymphoma and Leukemia Molecular Profiling ProjectSingapore

PTCL subtype and ENKTL cases with acceptable GEP

Lymphoma subtypes

o

f c

as

es

n=372 cases

PTCL- subtypes

Gene expression profiling data was generated on HG U133 plus 2 arrays ( Affymetrix Inc)

Refinement of molecular diagnostic signatures for PTCL subgroups

Relative Level of Expression (x median value)

Unique molecular signatures were identified for major PTCL entities

Relative Level of Expression (x median value)

AITL ALK- NKALK+

ALCL

TATTL

ENKTL

PTCL-NOS

Blood 2014 May 8123(19)2915-23Lymphoma and Leukemia Molecular Profiling Project (LLMPP) initiative

-of 152 PTCL-NOS cases a subset of cases were classified into

i AITL [14]

ii ALK(-)ALCL [11]

iii ATLL [03]

iv - PTCL [09]

- Of 117 AITL cases 26 cases (22) changed to PTCL-NOS

Evaluation of pathological vs molecular diagnosis

Blood 2014 May 8123(19)2915-23

ALK(+) ALCL

mdash MYC induced gene signaturemdash Proliferation signaturemdash NF-B target signature

mdash IL10 induced signaturemdash STAT3 signaturemdash Treg gene signaturemdash Presence of B cellsmdash HIF-alpha induced gene signature

ALK(-)ALCL

ALK(-)ALCL

mdash Proliferation signature mdash MYC induced gene signaturemdash IRF4 induced gene signaturemdash Absence of TCR signaling molecules

Gene set enrichment analysis

Gene signaturepathway enrichment summary in ALK(-)ALCL

ALK(-) ALCL is molecularly distinct from PTCL-NOS and ALK(+)ALCL

Re-classified from PTCL-NOS

ALKALK

ALK(+) ALCL ALK(-) ALCL PTCL-NOS

Blood 2014 May 8123(19)2915-23

Robust molecular signature for ALK(-)ALCL

Parilla Castellar et al Blood 2014August 28 124(9)1473-1480

DUSP22 and TP63 rearrangements in ALK- ALCL

NFkB2 GSP5

NFkB2 GSP54

NCOR2 GSP99

PABPC4 GSP50

ROS1

TYK2

ROS1

TYK2

Novel fusions combining a transcription factor

(NFkB2 or NCOR2) with a tyrosine kinase (ROS1

or TYK2)

Crescenzo and Abate etal Cancer Cell 2015

JAKSTAT3 pathway activation through

mutations and fusion transcripts

JAK1 and STAT3 mutations

₋ AITL₋ ATLL₋ ALK(-)ALCL₋ ALK(+)ALCL₋ NKCL₋ -PTCL

n=251 n=121

32 PTCL-NOS

WHO recognized TNK tumor subtypes

One-third of PTCL-NOS cases were not molecularly classified into WHO recognized PTCL entities

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

SPECS Strategic Partnering to Evaluate Cancer SignaturesiPTCL International peripheral T-cell lymphomaLLMPP Lymphoma and Leukemia Molecular Profiling ProjectSingapore

PTCL subtype and ENKTL cases with acceptable GEP

Lymphoma subtypes

o

f c

as

es

n=372 cases

PTCL- subtypes

Gene expression profiling data was generated on HG U133 plus 2 arrays ( Affymetrix Inc)

Refinement of molecular diagnostic signatures for PTCL subgroups

Relative Level of Expression (x median value)

Unique molecular signatures were identified for major PTCL entities

Relative Level of Expression (x median value)

AITL ALK- NKALK+

ALCL

TATTL

ENKTL

PTCL-NOS

Blood 2014 May 8123(19)2915-23Lymphoma and Leukemia Molecular Profiling Project (LLMPP) initiative

-of 152 PTCL-NOS cases a subset of cases were classified into

i AITL [14]

ii ALK(-)ALCL [11]

iii ATLL [03]

iv - PTCL [09]

- Of 117 AITL cases 26 cases (22) changed to PTCL-NOS

Evaluation of pathological vs molecular diagnosis

Blood 2014 May 8123(19)2915-23

ALK(+) ALCL

mdash MYC induced gene signaturemdash Proliferation signaturemdash NF-B target signature

mdash IL10 induced signaturemdash STAT3 signaturemdash Treg gene signaturemdash Presence of B cellsmdash HIF-alpha induced gene signature

ALK(-)ALCL

ALK(-)ALCL

mdash Proliferation signature mdash MYC induced gene signaturemdash IRF4 induced gene signaturemdash Absence of TCR signaling molecules

Gene set enrichment analysis

Gene signaturepathway enrichment summary in ALK(-)ALCL

ALK(-) ALCL is molecularly distinct from PTCL-NOS and ALK(+)ALCL

Re-classified from PTCL-NOS

ALKALK

ALK(+) ALCL ALK(-) ALCL PTCL-NOS

Blood 2014 May 8123(19)2915-23

Robust molecular signature for ALK(-)ALCL

Parilla Castellar et al Blood 2014August 28 124(9)1473-1480

DUSP22 and TP63 rearrangements in ALK- ALCL

NFkB2 GSP5

NFkB2 GSP54

NCOR2 GSP99

PABPC4 GSP50

ROS1

TYK2

ROS1

TYK2

Novel fusions combining a transcription factor

(NFkB2 or NCOR2) with a tyrosine kinase (ROS1

or TYK2)

Crescenzo and Abate etal Cancer Cell 2015

JAKSTAT3 pathway activation through

mutations and fusion transcripts

JAK1 and STAT3 mutations

₋ AITL₋ ATLL₋ ALK(-)ALCL₋ ALK(+)ALCL₋ NKCL₋ -PTCL

n=251 n=121

32 PTCL-NOS

WHO recognized TNK tumor subtypes

One-third of PTCL-NOS cases were not molecularly classified into WHO recognized PTCL entities

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

Refinement of molecular diagnostic signatures for PTCL subgroups

Relative Level of Expression (x median value)

Unique molecular signatures were identified for major PTCL entities

Relative Level of Expression (x median value)

AITL ALK- NKALK+

ALCL

TATTL

ENKTL

PTCL-NOS

Blood 2014 May 8123(19)2915-23Lymphoma and Leukemia Molecular Profiling Project (LLMPP) initiative

-of 152 PTCL-NOS cases a subset of cases were classified into

i AITL [14]

ii ALK(-)ALCL [11]

iii ATLL [03]

iv - PTCL [09]

- Of 117 AITL cases 26 cases (22) changed to PTCL-NOS

Evaluation of pathological vs molecular diagnosis

Blood 2014 May 8123(19)2915-23

ALK(+) ALCL

mdash MYC induced gene signaturemdash Proliferation signaturemdash NF-B target signature

mdash IL10 induced signaturemdash STAT3 signaturemdash Treg gene signaturemdash Presence of B cellsmdash HIF-alpha induced gene signature

ALK(-)ALCL

ALK(-)ALCL

mdash Proliferation signature mdash MYC induced gene signaturemdash IRF4 induced gene signaturemdash Absence of TCR signaling molecules

Gene set enrichment analysis

Gene signaturepathway enrichment summary in ALK(-)ALCL

ALK(-) ALCL is molecularly distinct from PTCL-NOS and ALK(+)ALCL

Re-classified from PTCL-NOS

ALKALK

ALK(+) ALCL ALK(-) ALCL PTCL-NOS

Blood 2014 May 8123(19)2915-23

Robust molecular signature for ALK(-)ALCL

Parilla Castellar et al Blood 2014August 28 124(9)1473-1480

DUSP22 and TP63 rearrangements in ALK- ALCL

NFkB2 GSP5

NFkB2 GSP54

NCOR2 GSP99

PABPC4 GSP50

ROS1

TYK2

ROS1

TYK2

Novel fusions combining a transcription factor

(NFkB2 or NCOR2) with a tyrosine kinase (ROS1

or TYK2)

Crescenzo and Abate etal Cancer Cell 2015

JAKSTAT3 pathway activation through

mutations and fusion transcripts

JAK1 and STAT3 mutations

₋ AITL₋ ATLL₋ ALK(-)ALCL₋ ALK(+)ALCL₋ NKCL₋ -PTCL

n=251 n=121

32 PTCL-NOS

WHO recognized TNK tumor subtypes

One-third of PTCL-NOS cases were not molecularly classified into WHO recognized PTCL entities

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

-of 152 PTCL-NOS cases a subset of cases were classified into

i AITL [14]

ii ALK(-)ALCL [11]

iii ATLL [03]

iv - PTCL [09]

- Of 117 AITL cases 26 cases (22) changed to PTCL-NOS

Evaluation of pathological vs molecular diagnosis

Blood 2014 May 8123(19)2915-23

ALK(+) ALCL

mdash MYC induced gene signaturemdash Proliferation signaturemdash NF-B target signature

mdash IL10 induced signaturemdash STAT3 signaturemdash Treg gene signaturemdash Presence of B cellsmdash HIF-alpha induced gene signature

ALK(-)ALCL

ALK(-)ALCL

mdash Proliferation signature mdash MYC induced gene signaturemdash IRF4 induced gene signaturemdash Absence of TCR signaling molecules

Gene set enrichment analysis

Gene signaturepathway enrichment summary in ALK(-)ALCL

ALK(-) ALCL is molecularly distinct from PTCL-NOS and ALK(+)ALCL

Re-classified from PTCL-NOS

ALKALK

ALK(+) ALCL ALK(-) ALCL PTCL-NOS

Blood 2014 May 8123(19)2915-23

Robust molecular signature for ALK(-)ALCL

Parilla Castellar et al Blood 2014August 28 124(9)1473-1480

DUSP22 and TP63 rearrangements in ALK- ALCL

NFkB2 GSP5

NFkB2 GSP54

NCOR2 GSP99

PABPC4 GSP50

ROS1

TYK2

ROS1

TYK2

Novel fusions combining a transcription factor

(NFkB2 or NCOR2) with a tyrosine kinase (ROS1

or TYK2)

Crescenzo and Abate etal Cancer Cell 2015

JAKSTAT3 pathway activation through

mutations and fusion transcripts

JAK1 and STAT3 mutations

₋ AITL₋ ATLL₋ ALK(-)ALCL₋ ALK(+)ALCL₋ NKCL₋ -PTCL

n=251 n=121

32 PTCL-NOS

WHO recognized TNK tumor subtypes

One-third of PTCL-NOS cases were not molecularly classified into WHO recognized PTCL entities

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

ALK(+) ALCL

mdash MYC induced gene signaturemdash Proliferation signaturemdash NF-B target signature

mdash IL10 induced signaturemdash STAT3 signaturemdash Treg gene signaturemdash Presence of B cellsmdash HIF-alpha induced gene signature

ALK(-)ALCL

ALK(-)ALCL

mdash Proliferation signature mdash MYC induced gene signaturemdash IRF4 induced gene signaturemdash Absence of TCR signaling molecules

Gene set enrichment analysis

Gene signaturepathway enrichment summary in ALK(-)ALCL

ALK(-) ALCL is molecularly distinct from PTCL-NOS and ALK(+)ALCL

Re-classified from PTCL-NOS

ALKALK

ALK(+) ALCL ALK(-) ALCL PTCL-NOS

Blood 2014 May 8123(19)2915-23

Robust molecular signature for ALK(-)ALCL

Parilla Castellar et al Blood 2014August 28 124(9)1473-1480

DUSP22 and TP63 rearrangements in ALK- ALCL

NFkB2 GSP5

NFkB2 GSP54

NCOR2 GSP99

PABPC4 GSP50

ROS1

TYK2

ROS1

TYK2

Novel fusions combining a transcription factor

(NFkB2 or NCOR2) with a tyrosine kinase (ROS1

or TYK2)

Crescenzo and Abate etal Cancer Cell 2015

JAKSTAT3 pathway activation through

mutations and fusion transcripts

JAK1 and STAT3 mutations

₋ AITL₋ ATLL₋ ALK(-)ALCL₋ ALK(+)ALCL₋ NKCL₋ -PTCL

n=251 n=121

32 PTCL-NOS

WHO recognized TNK tumor subtypes

One-third of PTCL-NOS cases were not molecularly classified into WHO recognized PTCL entities

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

Parilla Castellar et al Blood 2014August 28 124(9)1473-1480

DUSP22 and TP63 rearrangements in ALK- ALCL

NFkB2 GSP5

NFkB2 GSP54

NCOR2 GSP99

PABPC4 GSP50

ROS1

TYK2

ROS1

TYK2

Novel fusions combining a transcription factor

(NFkB2 or NCOR2) with a tyrosine kinase (ROS1

or TYK2)

Crescenzo and Abate etal Cancer Cell 2015

JAKSTAT3 pathway activation through

mutations and fusion transcripts

JAK1 and STAT3 mutations

₋ AITL₋ ATLL₋ ALK(-)ALCL₋ ALK(+)ALCL₋ NKCL₋ -PTCL

n=251 n=121

32 PTCL-NOS

WHO recognized TNK tumor subtypes

One-third of PTCL-NOS cases were not molecularly classified into WHO recognized PTCL entities

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

NFkB2 GSP5

NFkB2 GSP54

NCOR2 GSP99

PABPC4 GSP50

ROS1

TYK2

ROS1

TYK2

Novel fusions combining a transcription factor

(NFkB2 or NCOR2) with a tyrosine kinase (ROS1

or TYK2)

Crescenzo and Abate etal Cancer Cell 2015

JAKSTAT3 pathway activation through

mutations and fusion transcripts

JAK1 and STAT3 mutations

₋ AITL₋ ATLL₋ ALK(-)ALCL₋ ALK(+)ALCL₋ NKCL₋ -PTCL

n=251 n=121

32 PTCL-NOS

WHO recognized TNK tumor subtypes

One-third of PTCL-NOS cases were not molecularly classified into WHO recognized PTCL entities

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

₋ AITL₋ ATLL₋ ALK(-)ALCL₋ ALK(+)ALCL₋ NKCL₋ -PTCL

n=251 n=121

32 PTCL-NOS

WHO recognized TNK tumor subtypes

One-third of PTCL-NOS cases were not molecularly classified into WHO recognized PTCL entities

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

GATA3Unclassifiable

TBX21

37 0920 14149 208

nmedian OS

(years)

Time (years)

Pro

po

rtio

n (

OS

)

p=001

(B)

PTCL-NOS can be further divided two major subgroups

(A)

Pro

bab

ilit

y

(LO

OC

V)

TBX21

GATA3

Probability in TBX21 subgroup

Probability in GATA3 subgroup

TBX21 Unclassifiable GATA3

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

Tianjiao Wang et al Blood 20141233007-3015

GATA3 expression identifies a subset of

PTCL NOS with inferior survival

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

T-bet expression in Chinese PTCL cohort (n=142)

Ren YL etal Am J Clin Pathol 2012 Sep138(3)435-47

AITL

PTCL-NOS

TBX21 expression by Immunohistochemistry is

Predictive of survival in PTCL

p=02 p=005

Quartile

(D)

HampE CD3 TIA1

(B)

TIA1HampE CD3

(C)

Pro

po

rtio

n

Time (years)Time (years)

Cytotoxic

Pan-B

plasma-cell

Immunoglobulin

Cytotoxic- plasma

cell signature

sig

na

ture

Q1Q2Q3Q4

Q4Q1+Q2+Q3

OS in TBX21 subgroupOS in TBX21 subgroupQ1 Q2 Q3 Q4

Tumor microenvironment significantly influences the prognosis in TBX21 subgroup of PTCL-NOS

Blood 2014 May 8123(19)2915-23

University of Nebraska Medical Center

Training 41

Validation 42

Samples divided into Training

andvalidation set

Cases divided to minimize OS bias

Survival model Creation

P53 upregulatedCytotoxic T

Monocytic

B-cell

Other gene signature

AITL OS in different cohorts

International PTCL consortiumEurope (French AITL series)Europe (Italian AITL seriesLLMPP seriesAsian Singapore

10

08

06

04

02

00

2 4 6 8 10 12 14

Time (years)Time (years)

Time (years)

Pro

po

rtio

n

Pro

po

rtio

n

Pro

po

rtio

n

OS in training set10

08

06

04

02

00 Plt0001

Survival model creation in AITL

Signature Cluster Effect of high expression

Trainingp-value

Validation p-value

p53 upregulated signature Poor prognosis 0001 0014

Cytotoxic signature Poor prognosis 0005 0046

Monocyticdendritic signature Poor prognosis 0011 0010

B- cell signatureGood prognosis 0002 0017

Quartile

p=0004

Validation set

Survival prediction on AITL role of tumor microenvironment

Tumor microenvironment significantly influences the prognosis in AITL

Role of macrophages (M1) vs (M2) and dendritic cells are being investigated

10

08

06

04

02

00

Training set

Plt0001

IDH2 mutation is specifically associated with molecularly defined AITL cases

Chao etal ( under review)

RhoA mutation map in PTCL

GTPMg++-binding ldquoboxesrdquo

PKNPRK1 binding site

Effector region ldquoSwitch Irdquo

AITL G17E case includes an S26R mutation in same clone

^ K18M major clone has G17V minor clone

PTCL NOS

ALCL ALK-

G17V

G17E

x27

K18M^

S26R

G17V x10

D120G K135T

number ( of screened)

G17 S26 Other

AITL (n=39)deg 28 (718) 0 1 (26)^

PTCL NOS (n=41)

Tbx21 (n=19) 5 (263) 1 (53) 0

Gata3 (n=12) 2 (182) 0 0

Unclassified (n=10)deg 3 (333) 0 0

ALCL ALK- (n=12) 0 0 1 (83)

STAT3 and 5B mutations identified in NK or γδ-T cell derived lymphomas

Kucuk C Nat Commun 2015 Jan 1466025

Cell Membrane

IL2

Extracellular Space

IL2Rβ

IL2Rγα

IL2Rγ

JAK12 P

Cytoplasm

Nuclear Membrane Nuclear Membrane

STAT5B

STAT5B

STAT5B

STAT5B

P

P

P

STAT3

AZD1480

STAT3 STAT3

DNA

N642H

bullTarget (IL2Rα mir155hg BCL-XLhellip) transcription

bullPromotion of cell growth and survival

P

P

6 NKTCLs

46 γδ-PTCLs

6 NKTCLs

35 γδ-PTCLs

Increase affinity

prolonged association

Increase target

site

occupancy

P

P

Cell-of-origin for PTCL subgroups Can that be assigned

Adapte

d f

rom

OS

hea a

nd P

aul 2

010

Scie

nce

AITL

PTCL-GATA3Th2 subgroup

PTCL-NOSTh1 subgroup

ALCL (ALK+)

ALCL (ALK-)

ATLL

T PTCL

Laurence de Leval and Philippe Gaulard Blood 20141232909-2910

LAB MEMBERS

Tim McKeithan Andrew Canonn

Javeed Iqbal Zhongfeng Liu

Alyssa Bouska Shaungping Guo

Can Kucuk Karen Deffenbacher

Xiaozhou Hu Cuiling Liu

Bei Jiang

Weiwei Zhang

Chao Wang

Joe Rohr

Cindy Lachel

Yuping Li

Xinhua Wang

Kai Fu

Tim Greiner

Dennis Weisenburger

Julie Vose

I-PTCL

LLMPP

Nordic and ACT

Sichuan University

Singapore

Hong Kong

Iqbal Lab

University of Nebraska Medical Center

Training 41

Validation 42

Samples divided into Training

andvalidation set

Cases divided to minimize OS bias

Survival model Creation

P53 upregulatedCytotoxic T

Monocytic

B-cell

Other gene signature

AITL OS in different cohorts

International PTCL consortiumEurope (French AITL series)Europe (Italian AITL seriesLLMPP seriesAsian Singapore

10

08

06

04

02

00

2 4 6 8 10 12 14

Time (years)Time (years)

Time (years)

Pro

po

rtio

n

Pro

po

rtio

n

Pro

po

rtio

n

OS in training set10

08

06

04

02

00 Plt0001

Survival model creation in AITL

Signature Cluster Effect of high expression

Trainingp-value

Validation p-value

p53 upregulated signature Poor prognosis 0001 0014

Cytotoxic signature Poor prognosis 0005 0046

Monocyticdendritic signature Poor prognosis 0011 0010

B- cell signatureGood prognosis 0002 0017

Quartile

p=0004

Validation set

Survival prediction on AITL role of tumor microenvironment

Tumor microenvironment significantly influences the prognosis in AITL

Role of macrophages (M1) vs (M2) and dendritic cells are being investigated

10

08

06

04

02

00

Training set

Plt0001

IDH2 mutation is specifically associated with molecularly defined AITL cases

Chao etal ( under review)

RhoA mutation map in PTCL

GTPMg++-binding ldquoboxesrdquo

PKNPRK1 binding site

Effector region ldquoSwitch Irdquo

AITL G17E case includes an S26R mutation in same clone

^ K18M major clone has G17V minor clone

PTCL NOS

ALCL ALK-

G17V

G17E

x27

K18M^

S26R

G17V x10

D120G K135T

number ( of screened)

G17 S26 Other

AITL (n=39)deg 28 (718) 0 1 (26)^

PTCL NOS (n=41)

Tbx21 (n=19) 5 (263) 1 (53) 0

Gata3 (n=12) 2 (182) 0 0

Unclassified (n=10)deg 3 (333) 0 0

ALCL ALK- (n=12) 0 0 1 (83)

STAT3 and 5B mutations identified in NK or γδ-T cell derived lymphomas

Kucuk C Nat Commun 2015 Jan 1466025

Cell Membrane

IL2

Extracellular Space

IL2Rβ

IL2Rγα

IL2Rγ

JAK12 P

Cytoplasm

Nuclear Membrane Nuclear Membrane

STAT5B

STAT5B

STAT5B

STAT5B

P

P

P

STAT3

AZD1480

STAT3 STAT3

DNA

N642H

bullTarget (IL2Rα mir155hg BCL-XLhellip) transcription

bullPromotion of cell growth and survival

P

P

6 NKTCLs

46 γδ-PTCLs

6 NKTCLs

35 γδ-PTCLs

Increase affinity

prolonged association

Increase target

site

occupancy

P

P

Cell-of-origin for PTCL subgroups Can that be assigned

Adapte

d f

rom

OS

hea a

nd P

aul 2

010

Scie

nce

AITL

PTCL-GATA3Th2 subgroup

PTCL-NOSTh1 subgroup

ALCL (ALK+)

ALCL (ALK-)

ATLL

T PTCL

Laurence de Leval and Philippe Gaulard Blood 20141232909-2910

LAB MEMBERS

Tim McKeithan Andrew Canonn

Javeed Iqbal Zhongfeng Liu

Alyssa Bouska Shaungping Guo

Can Kucuk Karen Deffenbacher

Xiaozhou Hu Cuiling Liu

Bei Jiang

Weiwei Zhang

Chao Wang

Joe Rohr

Cindy Lachel

Yuping Li

Xinhua Wang

Kai Fu

Tim Greiner

Dennis Weisenburger

Julie Vose

I-PTCL

LLMPP

Nordic and ACT

Sichuan University

Singapore

Hong Kong

Iqbal Lab

Signature Cluster Effect of high expression

Trainingp-value

Validation p-value

p53 upregulated signature Poor prognosis 0001 0014

Cytotoxic signature Poor prognosis 0005 0046

Monocyticdendritic signature Poor prognosis 0011 0010

B- cell signatureGood prognosis 0002 0017

Quartile

p=0004

Validation set

Survival prediction on AITL role of tumor microenvironment

Tumor microenvironment significantly influences the prognosis in AITL

Role of macrophages (M1) vs (M2) and dendritic cells are being investigated

10

08

06

04

02

00

Training set

Plt0001

IDH2 mutation is specifically associated with molecularly defined AITL cases

Chao etal ( under review)

RhoA mutation map in PTCL

GTPMg++-binding ldquoboxesrdquo

PKNPRK1 binding site

Effector region ldquoSwitch Irdquo

AITL G17E case includes an S26R mutation in same clone

^ K18M major clone has G17V minor clone

PTCL NOS

ALCL ALK-

G17V

G17E

x27

K18M^

S26R

G17V x10

D120G K135T

number ( of screened)

G17 S26 Other

AITL (n=39)deg 28 (718) 0 1 (26)^

PTCL NOS (n=41)

Tbx21 (n=19) 5 (263) 1 (53) 0

Gata3 (n=12) 2 (182) 0 0

Unclassified (n=10)deg 3 (333) 0 0

ALCL ALK- (n=12) 0 0 1 (83)

STAT3 and 5B mutations identified in NK or γδ-T cell derived lymphomas

Kucuk C Nat Commun 2015 Jan 1466025

Cell Membrane

IL2

Extracellular Space

IL2Rβ

IL2Rγα

IL2Rγ

JAK12 P

Cytoplasm

Nuclear Membrane Nuclear Membrane

STAT5B

STAT5B

STAT5B

STAT5B

P

P

P

STAT3

AZD1480

STAT3 STAT3

DNA

N642H

bullTarget (IL2Rα mir155hg BCL-XLhellip) transcription

bullPromotion of cell growth and survival

P

P

6 NKTCLs

46 γδ-PTCLs

6 NKTCLs

35 γδ-PTCLs

Increase affinity

prolonged association

Increase target

site

occupancy

P

P

Cell-of-origin for PTCL subgroups Can that be assigned

Adapte

d f

rom

OS

hea a

nd P

aul 2

010

Scie

nce

AITL

PTCL-GATA3Th2 subgroup

PTCL-NOSTh1 subgroup

ALCL (ALK+)

ALCL (ALK-)

ATLL

T PTCL

Laurence de Leval and Philippe Gaulard Blood 20141232909-2910

LAB MEMBERS

Tim McKeithan Andrew Canonn

Javeed Iqbal Zhongfeng Liu

Alyssa Bouska Shaungping Guo

Can Kucuk Karen Deffenbacher

Xiaozhou Hu Cuiling Liu

Bei Jiang

Weiwei Zhang

Chao Wang

Joe Rohr

Cindy Lachel

Yuping Li

Xinhua Wang

Kai Fu

Tim Greiner

Dennis Weisenburger

Julie Vose

I-PTCL

LLMPP

Nordic and ACT

Sichuan University

Singapore

Hong Kong

Iqbal Lab

IDH2 mutation is specifically associated with molecularly defined AITL cases

Chao etal ( under review)

RhoA mutation map in PTCL

GTPMg++-binding ldquoboxesrdquo

PKNPRK1 binding site

Effector region ldquoSwitch Irdquo

AITL G17E case includes an S26R mutation in same clone

^ K18M major clone has G17V minor clone

PTCL NOS

ALCL ALK-

G17V

G17E

x27

K18M^

S26R

G17V x10

D120G K135T

number ( of screened)

G17 S26 Other

AITL (n=39)deg 28 (718) 0 1 (26)^

PTCL NOS (n=41)

Tbx21 (n=19) 5 (263) 1 (53) 0

Gata3 (n=12) 2 (182) 0 0

Unclassified (n=10)deg 3 (333) 0 0

ALCL ALK- (n=12) 0 0 1 (83)

STAT3 and 5B mutations identified in NK or γδ-T cell derived lymphomas

Kucuk C Nat Commun 2015 Jan 1466025

Cell Membrane

IL2

Extracellular Space

IL2Rβ

IL2Rγα

IL2Rγ

JAK12 P

Cytoplasm

Nuclear Membrane Nuclear Membrane

STAT5B

STAT5B

STAT5B

STAT5B

P

P

P

STAT3

AZD1480

STAT3 STAT3

DNA

N642H

bullTarget (IL2Rα mir155hg BCL-XLhellip) transcription

bullPromotion of cell growth and survival

P

P

6 NKTCLs

46 γδ-PTCLs

6 NKTCLs

35 γδ-PTCLs

Increase affinity

prolonged association

Increase target

site

occupancy

P

P

Cell-of-origin for PTCL subgroups Can that be assigned

Adapte

d f

rom

OS

hea a

nd P

aul 2

010

Scie

nce

AITL

PTCL-GATA3Th2 subgroup

PTCL-NOSTh1 subgroup

ALCL (ALK+)

ALCL (ALK-)

ATLL

T PTCL

Laurence de Leval and Philippe Gaulard Blood 20141232909-2910

LAB MEMBERS

Tim McKeithan Andrew Canonn

Javeed Iqbal Zhongfeng Liu

Alyssa Bouska Shaungping Guo

Can Kucuk Karen Deffenbacher

Xiaozhou Hu Cuiling Liu

Bei Jiang

Weiwei Zhang

Chao Wang

Joe Rohr

Cindy Lachel

Yuping Li

Xinhua Wang

Kai Fu

Tim Greiner

Dennis Weisenburger

Julie Vose

I-PTCL

LLMPP

Nordic and ACT

Sichuan University

Singapore

Hong Kong

Iqbal Lab

RhoA mutation map in PTCL

GTPMg++-binding ldquoboxesrdquo

PKNPRK1 binding site

Effector region ldquoSwitch Irdquo

AITL G17E case includes an S26R mutation in same clone

^ K18M major clone has G17V minor clone

PTCL NOS

ALCL ALK-

G17V

G17E

x27

K18M^

S26R

G17V x10

D120G K135T

number ( of screened)

G17 S26 Other

AITL (n=39)deg 28 (718) 0 1 (26)^

PTCL NOS (n=41)

Tbx21 (n=19) 5 (263) 1 (53) 0

Gata3 (n=12) 2 (182) 0 0

Unclassified (n=10)deg 3 (333) 0 0

ALCL ALK- (n=12) 0 0 1 (83)

STAT3 and 5B mutations identified in NK or γδ-T cell derived lymphomas

Kucuk C Nat Commun 2015 Jan 1466025

Cell Membrane

IL2

Extracellular Space

IL2Rβ

IL2Rγα

IL2Rγ

JAK12 P

Cytoplasm

Nuclear Membrane Nuclear Membrane

STAT5B

STAT5B

STAT5B

STAT5B

P

P

P

STAT3

AZD1480

STAT3 STAT3

DNA

N642H

bullTarget (IL2Rα mir155hg BCL-XLhellip) transcription

bullPromotion of cell growth and survival

P

P

6 NKTCLs

46 γδ-PTCLs

6 NKTCLs

35 γδ-PTCLs

Increase affinity

prolonged association

Increase target

site

occupancy

P

P

Cell-of-origin for PTCL subgroups Can that be assigned

Adapte

d f

rom

OS

hea a

nd P

aul 2

010

Scie

nce

AITL

PTCL-GATA3Th2 subgroup

PTCL-NOSTh1 subgroup

ALCL (ALK+)

ALCL (ALK-)

ATLL

T PTCL

Laurence de Leval and Philippe Gaulard Blood 20141232909-2910

LAB MEMBERS

Tim McKeithan Andrew Canonn

Javeed Iqbal Zhongfeng Liu

Alyssa Bouska Shaungping Guo

Can Kucuk Karen Deffenbacher

Xiaozhou Hu Cuiling Liu

Bei Jiang

Weiwei Zhang

Chao Wang

Joe Rohr

Cindy Lachel

Yuping Li

Xinhua Wang

Kai Fu

Tim Greiner

Dennis Weisenburger

Julie Vose

I-PTCL

LLMPP

Nordic and ACT

Sichuan University

Singapore

Hong Kong

Iqbal Lab

STAT3 and 5B mutations identified in NK or γδ-T cell derived lymphomas

Kucuk C Nat Commun 2015 Jan 1466025

Cell Membrane

IL2

Extracellular Space

IL2Rβ

IL2Rγα

IL2Rγ

JAK12 P

Cytoplasm

Nuclear Membrane Nuclear Membrane

STAT5B

STAT5B

STAT5B

STAT5B

P

P

P

STAT3

AZD1480

STAT3 STAT3

DNA

N642H

bullTarget (IL2Rα mir155hg BCL-XLhellip) transcription

bullPromotion of cell growth and survival

P

P

6 NKTCLs

46 γδ-PTCLs

6 NKTCLs

35 γδ-PTCLs

Increase affinity

prolonged association

Increase target

site

occupancy

P

P

Cell-of-origin for PTCL subgroups Can that be assigned

Adapte

d f

rom

OS

hea a

nd P

aul 2

010

Scie

nce

AITL

PTCL-GATA3Th2 subgroup

PTCL-NOSTh1 subgroup

ALCL (ALK+)

ALCL (ALK-)

ATLL

T PTCL

Laurence de Leval and Philippe Gaulard Blood 20141232909-2910

LAB MEMBERS

Tim McKeithan Andrew Canonn

Javeed Iqbal Zhongfeng Liu

Alyssa Bouska Shaungping Guo

Can Kucuk Karen Deffenbacher

Xiaozhou Hu Cuiling Liu

Bei Jiang

Weiwei Zhang

Chao Wang

Joe Rohr

Cindy Lachel

Yuping Li

Xinhua Wang

Kai Fu

Tim Greiner

Dennis Weisenburger

Julie Vose

I-PTCL

LLMPP

Nordic and ACT

Sichuan University

Singapore

Hong Kong

Iqbal Lab

Cell Membrane

IL2

Extracellular Space

IL2Rβ

IL2Rγα

IL2Rγ

JAK12 P

Cytoplasm

Nuclear Membrane Nuclear Membrane

STAT5B

STAT5B

STAT5B

STAT5B

P

P

P

STAT3

AZD1480

STAT3 STAT3

DNA

N642H

bullTarget (IL2Rα mir155hg BCL-XLhellip) transcription

bullPromotion of cell growth and survival

P

P

6 NKTCLs

46 γδ-PTCLs

6 NKTCLs

35 γδ-PTCLs

Increase affinity

prolonged association

Increase target

site

occupancy

P

P

Cell-of-origin for PTCL subgroups Can that be assigned

Adapte

d f

rom

OS

hea a

nd P

aul 2

010

Scie

nce

AITL

PTCL-GATA3Th2 subgroup

PTCL-NOSTh1 subgroup

ALCL (ALK+)

ALCL (ALK-)

ATLL

T PTCL

Laurence de Leval and Philippe Gaulard Blood 20141232909-2910

LAB MEMBERS

Tim McKeithan Andrew Canonn

Javeed Iqbal Zhongfeng Liu

Alyssa Bouska Shaungping Guo

Can Kucuk Karen Deffenbacher

Xiaozhou Hu Cuiling Liu

Bei Jiang

Weiwei Zhang

Chao Wang

Joe Rohr

Cindy Lachel

Yuping Li

Xinhua Wang

Kai Fu

Tim Greiner

Dennis Weisenburger

Julie Vose

I-PTCL

LLMPP

Nordic and ACT

Sichuan University

Singapore

Hong Kong

Iqbal Lab

Cell-of-origin for PTCL subgroups Can that be assigned

Adapte

d f

rom

OS

hea a

nd P

aul 2

010

Scie

nce

AITL

PTCL-GATA3Th2 subgroup

PTCL-NOSTh1 subgroup

ALCL (ALK+)

ALCL (ALK-)

ATLL

T PTCL

Laurence de Leval and Philippe Gaulard Blood 20141232909-2910

LAB MEMBERS

Tim McKeithan Andrew Canonn

Javeed Iqbal Zhongfeng Liu

Alyssa Bouska Shaungping Guo

Can Kucuk Karen Deffenbacher

Xiaozhou Hu Cuiling Liu

Bei Jiang

Weiwei Zhang

Chao Wang

Joe Rohr

Cindy Lachel

Yuping Li

Xinhua Wang

Kai Fu

Tim Greiner

Dennis Weisenburger

Julie Vose

I-PTCL

LLMPP

Nordic and ACT

Sichuan University

Singapore

Hong Kong

Iqbal Lab

LAB MEMBERS

Tim McKeithan Andrew Canonn

Javeed Iqbal Zhongfeng Liu

Alyssa Bouska Shaungping Guo

Can Kucuk Karen Deffenbacher

Xiaozhou Hu Cuiling Liu

Bei Jiang

Weiwei Zhang

Chao Wang

Joe Rohr

Cindy Lachel

Yuping Li

Xinhua Wang

Kai Fu

Tim Greiner

Dennis Weisenburger

Julie Vose

I-PTCL

LLMPP

Nordic and ACT

Sichuan University

Singapore

Hong Kong

Iqbal Lab