Trisomy 14 and Leukemia

0165-4608/98/$19.00PII S0165-4608(98)00053-3

Cancer Genet Cytogenet 106:144–151 (1998)

Elsevier Science Inc., 1998655 Avenue of the Americas, New York, NY 10010

Trisomy 14 and Leukemia

K. S. Reddy

ABSTRACT:

A total of 11 cases with trisomy 14 as the sole abnormality were found in the database of alarge cytogenetic reference laboratory from 1993 to the present. Four of the 11 cases had an isochromo-some 14q. In 8 cases, the trisomy 14 was a mosaic cell line. Eight cases were diagnosed with myelodys-plasia, 2 cases had both myelodysplastic and myeloproliferative features similar to some atypicalchronic myeloid leukemia cases, and 1 case had acute myeloid leukemia of M1 or M2 type. Nine weremales and two females. The median age was 77 years. Referring physicians were contacted and clinical

information was available in only 8 cases. Survival ranged from 1 month to

z

3 years. An abnormal redcell morphology, such as elliptocytes or schistocytes or both, was observed in the majority of cases. Thisstudy along with the reported cases strengthens the hypothesis that trisomy 14 is a nonrandom cytoge-netic abnormality associated with myeloid malignancy. © Elsevier Science Inc., 1998

INTRODUCTION

Structural chromosome abnormalities are the majority ofnon-random changes in hemopoietic neoplasms, whileisolated chromosome gain (apart from trisomy 8) is ratherrare [1]. Trisomy 14 is an abnormality observed in hemato-logical disorders and is restricted mostly to myeloid disor-ders. In 40 reported myeloid malignancy cases, trisomy 14is the sole clonal change [2–23]. The majority of patientspresented with myelodysplastic syndrome (MDS), followedby acute myeloid leukemia (AML), and then atypical chronicmyeloid leukemia (aCML) (Ph-negative). The aCML casesalso have some myelodysplastic features. In this paper, thelargest series of trisomy 14 patients are described and asummary of published cases are tabulated to draw an asso-ciation between trisomy 14 and myeloid disorders.

CASE HISTORY

Patient 1

An 81-year-old man had refractory anemia for many years.He suffered a heart attack and aneurysm while on vaca-tion. A chromosome study was performed. His karyotypewas 46,XY,i(14)(q10)[2]/46,XY[28]. The patient was lost tofollow-up.

Patient 2

A 66-year-old man was sent for chromosome studies be-cause of persistent anemia for 6–8 months. The anemia

did not appear to be related to nutrition. He had no othermedical illness or surgery except for a left and right herni-orrhaphy. The only known exposures the patient had had

were to paint fumes and to cobalt for

z

3 minutes, 43 yearsearlier. He smoked cigarettes on and off for 20 years, butquit 2 years ago.

The complete blood count was white blood cells, 5,800/mm

3

; hemoglobin, 7.9 grams/dL; hemocrit, 24.2%; meancorpuscular volume, 101.4

m

m

3

; and platelets, 133,000/mm

3

. The differential included 60% neutrophils, 28%lymphocytes, 1% metamyelocytes, and 3% myelocytes.The peripheral smear had normal and some immaturewhite cell elements, myelocytes, some Pelgeroid-typecells, and an occasional blast. The bone marrow smearwas 75–90% cellular. Normoblasts, poorly differentiatederythroblasts, and many mitotic figures were present inthe marrow. Megakaryocytes were increased in number.There was a maturation arrest of myelopoiesis. The patienthad marked red blood cell morphology changes, particu-larly elliptocytes and tear drop cells. The patient probablyhad myelodysplastic syndrome. His bone marrow karyo-type was 46,XY,i(14)(q10)[20]. He has been on supportivecare since September 1997.

Patient 3

An 81-year-old man presented with persistent leukocyto-sis, mild anemia, and probable pulmonary vasculitis. Thepatient was evaluated for pulmonary symptoms and wasdiagnosed with pulmonary vasculitis (i.e., Wegener syn-drome) and treated with moderate doses of prednisone.He had a prior bleeding duodenal ulcer and a cholecys-tectomy.


3

; hemoglobin, 9.5 g/dL; hemocrit, 29.8%; platelets,253,000/mm

3

. The differential count was erythroid pre-

From Quest Diagnostics Inc., San Juan Capistrano, California,USA.

Address reprint requests to: Dr. Kavita S. Reddy, Cytogenetics,Quest Diagnostics Inc., 33608 Ortega Highway, San Juan Capis-trano, CA 92690-6130.

Received January 13, 1998; accepted March 17, 1998.


145

cursors, 6%; neutrophils and precursors, 85%; lympho-cytes, 7%; monocytes, 1%; and blasts, 1%. The peripheralblood showed neutrophilic leukocytosis. The neutrophilshad a relatively hypogranular appearance. Scattered lym-phocyte and erythroid precursors were present. Leukocy-tosis with a neutrophilia with normocytic anemia was ob-served. The size and shape of platelets showed variation.The blast population was

,

5%. The bone marrow wasmoderately hypercellular with dysgranulopoiesis. The di-agnosis was low-grade myelodysplastic syndrome with re-fractor anemia. His bone marrow karyotype was 47,XY,

1

14[29]/46,XY[1]. The patient has been on supportivecare since March 1997.

Patient 4

An 86-year-old woman presented with fatigue, dyspnea,bruisability, and gum bleeding. She had a history of coro-nary heart disease, degenerative joint disease, carpel tun-nel syndrome, cataract, and glaucoma. Ten years earlier,the patient had presented with mild anemia. Her anemia,leukopenia, and thrombocytopenia progressed in the suc-cessive years. She was diagnosed with immune-mediatedthrombocytopenia and was treated with prednisone, 30mg; vinblastine; and vincristine. A splenectomy was per-formed. Her pancytopenia persisted and she was diag-nosed with MDS. The complete blood count was whiteblood cells, 103,000/mm

3

; platelets, 44,000/mm

3

; hem-ocrit, 32.5%; hemoglobin, 11.3 g/dL; and mean corpuscu-lar hemaglobin, 32.7 pg/red cell. The differential was lym-phocytes, 34.34%; monocytes, 41.04%; and granulocytes,24.7%. The peripheral blood smear revealed moderateanisopoikilocytosis, mild to moderate macrocytosis, and anoccasional microsperocyte, schistocyte, and elliptocyte.

The bone marrow aspirate smear was hypercellularwith myeloid and megakaryocytic hyperplasia. The mega-karyocytes showed dysplastic forms and were of smallsize. The granulocytes were dysplastic, Pelgeroid and hy-pogranular forms, with no increase in blasts. Erythrocyticdysplasia was not seen. The bone marrow picture sug-gested MDS, but a diagnosis of chronic myeloproliferativedisorder could not be excluded. The bone marrow biopsywas hypercellular with a cellularity of 80%. The M

;

E ratiowas greater than 5

;

1. There was no evidence of fibrosis.Her bone marrow karyotype was 46,XX,i(14)(q10)[5]/46,XX[25]. The patient was lost to follow-up.

Patient 5

A 71-year-old woman presented with pancytopenia,odynophagia, and loss of weight. She had stopped smok-ing cigarettes 3 weeks earlier. She recalled a history ofanemia.


3

; hemoglobin, 8.4 g/dL; and hemocrit, 25.3%. Theplatelet count was 170,000/mm

3

. The differential countwas segmented neutrophils, 0.5%; monocytes, 6%; meta-myelocytes, 0.5%; myelocytes, 1%; promyelocytes, 0.5%;blasts, 50.5%; and lymphocytes, 30.5%. The red cellsshowed mild to moderate anisopoikilocytosis with a fewovalocytes and tear drop cells. The peripheral smearshowed marked neutropenia. The blasts were large, and

grainy with a single large nucleolus. No Auer rods or vacu-oles were present in the cytoplasm. The lymphocytes wereintermediate to large in size and many had small nucleoli.The abnormal platelets were large granular forms. Thebone marrow smear was hypercellular with a high per-centage of blasts and small lymphocytes. Erythroid matu-ration was normoblastic. The T- and B-cell marker studiesdid not show an abnormal lymphocytic population. Anabnormal population of myeloperoxidase positive andCD13, CD34, and CD38 positive cells consistent with acutemyelogenous M1 or M2 was detected. Her bone marrowkaryotype was 47,XX,

1

14. The patient was treated with

ara-c

and Idarubicin. Subsequent to the treatment she be-came neutropenic and had low platelets. She was placedon multiple antibiotics. Shortly thereafter she developedpneumonia and died.

Patient 6

A 72-year-old man developed gradual fatigue and leg painin the preceding year. He had an elevated white cell countand anemia. His past medical history included peptic ul-cers and partial gasterectomy. The patient was treatedwith prednisone of 25–100-mg strength. He was a heavysmoker of cigarettes and a heavy to moderate drinker of al-cohol.


3

; red blood cells, 2,200,000/mm

3

; hemoglobin, 8.1 g/dL;hemocrit, 25%; platelets, 104,000/mm

3

. The differentialcount was bands, 8%; granulocytes, 54%; lymphocytes,22%; monocytes, 2%; myelocytes, 10%; metamyelocytes,4%; and blasts, 10%. In the peripheral smear, moderatevariations in the size and shape of red cells and myeloidmaturation were seen. The morphology ranged from poly-chromatophilic macrocytes to hypochromic microcytes.Teardrop and occasional spherocytes were noted. Themarrow smear was quiet cellular with a heavy predomi-nance of myeloid precursors, although all stages of mye-loid and erythroid maturation were present. The bonemarrow examination revealed anemia with granulocyticleukocytosis. The hyperplastic marrow had predominantgranulocytic proliferation. The marrow’s iron stores weredecreased and reticulin content increased. The findings inthe peripheral blood and bone marrow were consistentwith chronic myelogenous leukemia. The bone marrowkaryotype was 47,XY,

1

14[14]/46,XY[16]. The patient dieda year later.

Patient 7

A 77-year-old man had dyspnea, fatigue, and pancyto-penia. The complete blood count was white blood cells,28,000/mm

3

; hemoglobin, 8.6 grams/dL; hemocrit, 23.4%;and platelets, 84,000/mm

3

. The differential count was seg-mented neutrophils, 48%; lymphocytes, 39%; monocytes,6%; and eosinophils, 7%. In the peripheral smear, therewere moderate ovalocytes, tear drop cells, and schisto-cytes. The bone marrow biopsy was hypercellular with adecrease in megakaryocytes. There was marked erythroidhyperplasia, with maturation into basophilic megaloblastswith fine vacuoles. The Prussian blue reaction demon-strated an increased amount of stored iron and frequent si-

146

K. S. Reddy

deroblasts. Megaloblastic dyspoiesis with ringed sidero-blasts consistent with myelodysplasia was observed. Thebone marrow karyotype was 47,XY,

1

14[5]/46,XY[25]. Thepatient was on maintenance therapy, and he had had threetransfusions. On February 12, 1997, his hemoglobin was8.7 g/dL and the platelet count was 45,000/mm

3

. He didnot require transfusion for several months. The patient hasdied, and the cause or date of his death is not known.

Patient 8

A 73-year-old male patient was a retired steel worker andpresented with chest pain. The patient did not drink alco-hol but smoked cigarettes for 17 years. He suffered frompeptic ulcers and had Billroth surgery and a BEZOR whenhe was 71 years old. Six years before presenting with chestpain, he had had TURP, cholecystectomy, and angio-plasty. His hemocrit was 39%, with microcytic indicesand a mean corpuscular volume of 72

m

m

3

. The whiteblood cell count was 18,600/mm

3

, basophils, 9%; andblasts, 1%. The platelet count was 957,000/mm

3

. The pa-tient appeared to have chronic myeloproliferative disordercharacterized by leukocytosis, thrombocytosis, and micro-cytic anemia. A peripheral smear demonstrated some vari-ation in the size and shape of red blood cells and a fewschistocytes were seen. Platelets were increased, and giantforms were seen. White cells were band forms and manypolymorphs. The bone marrow aspirate was hypercellularwith all stages of red and white cell maturation. Megakary-ocytes were present in numerous clumps. The overall im-pression was myeloproliferative disorder. The molecularBCR-ABL test did not detect a fusion message. The bonemarrow karyotype was 46,XY,i(14)(q10)[9]/46,XY[21]. Thepatient was not compliant with follow-up visits.

Patient 9

A 73-year-old man had myelodysplastic syndrome. Hisbone marrow karyotype was 47,XY,

1

14[11]/46,XY[18].The physician could not be contacted for clinical infor-mation.

Patient 10

A 78-year-old man had thrombocytopenia and no blasts.The bone marrow karyotype was 46,X,

2

Y,

1

14[2]/46,XY[17]. The patient had expired and the next to kin couldnot be traced to obtain consent for release of clinical infor-mation.

Patient 11

An 81-year-old man presented with anemia after a signifi-cant nose bleed. He did not drink alcohol or smoke ciga-rettes. His medical history included hypertension, chronicatrial fibrillation, discoid lupus, blindness in the left eyesecondary to detached retina, and glaucoma. The surgerieshe had had were hip replacements, left knee replacements,and removal of kidney stones, a partial left nephrectomyfor a cyst, and a right inguinal herniorrhaphy.

The complete blood picture was white blood cells,4210/mm

3

; hemoglobin, 10.5 g/dL; hemocrit, 31.1%; meancorpuscular volume, 98.1

m

m

3

; and platelets, 116,000/mm

3

. The differential count was segmented neutrophils,

58%; bands, 1%; lymphocytes, 34%; monocytes, 6%; andeosinophils, 1%. Moderate anisopoikilocytosis was ob-served. The bone marrow biopsy had moderate cellularitywith a reversal of the M

;

E ratio. Erythroid precursors pre-dominated; they exhibited megaloblastic maturation andincluded an increased number of early dysplastic forms.Myeloid elements were moderately decreased, exhibitedmaturation, and included increased numbers of earlyforms with promyelocytes and myelocytes. Myeloblastsconstituted less than 5% of the marrow. The marrow wasnormocellular with relative erythroid hyperplasia and in-creased numbers of immature myeloid forms. The diagno-sis was myelodysplastic syndrome with thrombocytope-nia. The bone marrow karyotype was 46,X,

2

Y,

1

14.Six months later, the patient was admitted with nausea

and vomiting. He was found to have cerebrovascular acci-dent. His stools were mahogany color, and the impressionwas that he also had gastrointestinal bleeding. He died thenext day.

MATERIALS AND METHODS

Unstimulated 24-hour and 48-hour cultures were initiatedon the bone marrow specimen received by the laboratory.The cultures were harvested and the slides GTG-banded.The chromosome findings were described according to theISCN 1995 guidelines [24].

DISCUSSION

The consistent primary trisomies in myeloid disorderswere 4, 6, 8, 9, 11, 13, 19, 21, 22 [1]. Tables 1 and 2 sum-marize the findings in the present study and the reportedcases. The total number of cases with myeloid disordersand trisomy 14 cited in the literature and this study was51 cases. The sex distribution was 33 males and 17 fe-males. The median age at diagnosis was 72 years andranged from 4 to 89 years. Trisomy 14 has been identifiedin disorders of the myeloid lineage such as myelodysplas-tic syndrome, 31/51 (61%). The MDS subtypes were 8/31(26%) refractory anemia (RA); 3/31 (10%) refractory ane-mia with ringed sideroblasts (RARS); 3/31 (10%) refrac-tory anemia with excess of blasts (RAEB); 4/31 (13%) re-fractory anemia with excess of blasts in transformation(RAEBT); 6/31 (19%) chronic myelomonocytic leukemia;and 2/31 (6%) aplastic anemia. Myeloproliferative disor-der (MPD) was present in 1/51 (2%) cases with trisomy 14.Philadelphia negative chronic myeloid leukemia with my-elodysplastic features was observed in 7/51 (14%) cases.Acute myeloid leukemia was found in 12/51 (24%) tri-somy 14 cases; of these cases, 1/12 (8%) was M1, 5/12(42%) belonged to the M2 subgroup, 1/12 (8%) was M1 orM2, 1/12 (8%) was M4, and 1/12 (8%) was M4 or M5. Inconclusion, most trisomy 14 cases have MDS at diagnosisfollowed by AML. The AML frequently appears to be M2subgroup and occasionally M1, M4, or M5 type. Onlythree cases of trisomy 14 were reported with lymphoidmalignancies such as large-cell immunoblastic lymphoma[15], large granular lymphocyte leukemia [25], and acutelymphoblastic leukemia [26].


147

Ten of the 51 cases had isochromosome for chromo-some 14 long arm and had MDS, MDS/MPD, AML, oraCML (Table 2). In the present study, there were four iso-chromosome 14q cases. The age (median 73.8 years), sexdistribution (10 males; 4 females), and survival (2–42

1

months) were not notably different from the other trisomy14 cases. Even the malignancy present in i(14)(q10) wasnot found to be more aggressive than that present in othertrisomy 14 cases (Table 2).

Mosaicism for trisomy 14 was found in 40/51 (78%)cases. The ratio of trisomy 14 cells did not correlate withthe seriousness of the disease (Table 2). However, in casesreported by Poirel et al. [21] and Mancini et al. [19], forwhich cytogenetic monitoring of the leukemia was docu-mented, the trisomy 14 clone disappeared at remission.Survival of trisomy 14 patients ranged from 1 month to75

1

months after diagnosis. The platelet count was highlyvariable in trisomy 14 cases, from 5 to 1044 (

3

10

3

/mm

3

).Elevated monocyte count (

.

10%) was observed in a pa-tient’s bone marrow in the present study and was alsofound in about half (7/13 patients in Table 2) of the casesin the literature with documentation.

Four cases [2, 11, 15, 19] diagnosed with trisomy 14and MDS, MDS-RAEB, MDS-RARS, and MDS-RAEB de-

veloped into AML in 22 months, into AML-M1 in 4months, into AML in 73 months, and into AML-M2 in 18months, respectively. Therefore, the advanced MDS caseswith RAEB developed AML earlier.

The biological basis of trisomy 14 and myeloid disor-ders is not known. There are two possibilities: (1) trisomy14 may be the consequence of genomic instability or (2)the higher copy number of 14 could be the key event inthe development of the malignancy. Two oncogenes

c-fos

and

AKT1

are mapped to chromosome 14. The

c-fos

ex-pression has not been significantly different in MDS andpatients with nonmalignant marrow disorders [27].

Red cell morphological changes such as elliptocytesand schistocytes in MDS have been described in four pub-lished reports [23, 28–30]. Boavida et al. [23] records ani(14)(q10) patient with marked elliptocytes and schisto-cytes but without a qualitative and quantitative differencein the key membrane proteins (spectrin, ankyrin, proteins4.1 and 4.2) responsible for elliptocytosis. They concludethat the red cell abnormalities may be secondary to the he-matological disorder. From a review of the literature andthe present study, 15/51 cases with trisomy 14 (Tables 1and 2) had anisopoikilocytosis, elliptocytes, or schisto-cyes. None had a documented family history of elliptocy-

Table 1

Summary of the cases with trisomy 14

Patient no.

Age(years)/sex Diagnosis Karyotype

Platelets (10

3

/mm

3

) and monocytes Survival

Red cell morphology

1 81/M MDS 46,XY,i(14)(q10)[2]/46,XY[28] NA NA NARA NA

2 66/M MDS 46,XY,i(14)(q10)[20] 1396%

3 months (supportive care)

Marked changes, anisopoikilocytosis, elliptocytosis, tear drop cells

3 81/M MDSRA

47,XY,

1

14[29]/46,XY[1] 2531%

9 months(supportive care)

Anisocytosis

4 86/F MDSCMMoL

46,XX,i(14)(q10)[5]/46,XX[25] 4441%

NA Moderate anisopoikilocytosis, few schistocytes, and elliptocytes

5 71/F AML 47,XX,

1

14[20] 175 1 month Mild ainisopoikilocytosisM1 orM2 6%

6 73/M MPD 46,XY,

1

14[14]/46,XY[16} 106 1 year Teardrop cells and few spherocytesaCML/MDS 2%

7 77/M MDS 47,XY,

1

14[5]/46,XY[25] 84 1–3 years Some ovalocytes and schistocytesRARS 6%

8 73/M MPD 46,XY,i(14)(q10)[9]/46,XY[21] 957 NA Few schistocytesaCML? 10%

9 73/M MDS 47,XY,

1

14[11]/46,XY[19] NA NA NANA

10 78/M Thrombocytopenia 46,X,

2

Y,

1

14[2]/46,XY[18] NA NA NANA

11 81/M MDS 46,X,

2

Y,

1

14[20] 116 6 months Moderateanisopoikilocytosis7%

Abbreviations:

M, male; F, female; MDS, myelodysplastic syndrome, RA, refractory anemia, RARS, refractory anemia with sideroblasts; MPD, myeloprolifer-ative disorder; aCML, atypical chronic myeloid leukemia; AML, acute myeloid leukemia (M1/M2 are subgroups); NA, not available.

148

K. S. Reddy

Tab

le 2

Su

mm

ary

of r

epor

ted

cas

es w

ith

tri

som

y 14

No.

Age

(yea

rs)/

sex

Dia

gnos

isK

aryo

typ

eP

late

lets

10

3

/mm

3

an

d m

onoc

ytes

[%

]S

urv

ival

Red

cel

l m

orp

hol

ogy

Ref

eren

ce

140

/FM

DS

47,X

X,

1

14[2

0%]/

46,X

X[8

0%]

NA

22 m

onth

s, A

ML

NA

Now

ell a

nd

Fin

an, 1

978

[2]

NA

278

/MP

h-v

e47

,XY

,

1

14[1

2]/4

6,X

Y[5

]29

1 m

onth

; die

d a

fter

surg

ery

for

aneu

rysm

NA

Sh

ash

aty

and

Bau

mil

ler,

19

80 [

3]C

ML

43

69/M

AM

L47

,XY

,

1

14[9

]/46

,XY

[8]

NA

14.5

mon

ths

(rem

issi

on,

then

rel

apse

)N

AL

i et

al.

, 198

3 [4

]M

4R

elap

se47

,XY

,

1

14[7

%]/

46,X

Y[9

3%]

NA

460

/FA

ML

47,X

X,

1

14[6

]/46

,XX

[1]

NA

NA

NA

Yu

nis

, 198

4 [5

]M

IN

A5

58/M

MP

D47

,XY

,

1

14[9

2%]/

46,X

Y[8

%]

NA

40 m

onth

sN

AM

ille

r et

al.

, 198

5N

A6

61/M

MD

S47

,XY

,

1

14[6

0%]/

46,X

Y[4

0%]

61P

arti

al r

emis

sion

al

ive

at 2

4 m

onth

sN

AH

ass

et a

l., 1

987

[7]

RA

EB

T47

,XY

,

1

14[8

0%]/

46,X

Y[2

0%]

NA

762

/FA

ML

46,X

X,i

(14q

)N

AN

AN

AM

elon

i-B

alli

et e

t al

.19

89

[8]

NA

881

/MA

ML

46,X

Y,i

(14q

)55

1P

arti

al r

emis

sion

,al

ive

at 4

mon

ths

NA

NA

948

/FA

ML

47,X

X,

1

1412

8/N

AA

live

at

5 m

onth

sN

orm

al10

64/M

aCM

L47

,XY

,

1

14[2

1]/4

6,X

Y[4

][at

3 a

nd

14

mon

ths]

114

18 m

onth

s; d

ied

of

GI

blee

dN

orm

alM

erte

ns

et a

l., 1

989

[9]

NA

1184

/FaC

ML

47,X

X,

1

14[1

1]/4

6,X

X,i

(14q

)[4]

/46,

X,i

(Xq)

[5]/

46,X

X[5

]21

0N

A49

mon

ths

NA

1278

/MaC

ML

47,X

Y,

1

14[9

]/46

,XY

[4]

153

Par

tial

rem

issi

on,

at 1

2 m

onth

s, d

ied

of s

epsi

s

NA

NA

1383

/FaC

ML

47,X

X,

1

14[2

9]5 N

orm

alP

arti

al r

emis

sion

, at

2 m

onth

s d

ied

of

mu

ltio

rgan

fai

lure

NA

1482

/MM

DS

47,X

Y,

1

14[6

]/46

,XY

[4]

NA

4 m

onth

s; d

ied

of

ren

alin

suff

icie

ncy

an

dp

neu

mon

ia

NA

Jott

eran

d-B

ella

mo

et a

l.,

1990

[10

]R

AN

A

1574

/MM

DS

RA

46,X

Y,i

(14q

)[11

]/46

,XY

[18]

1044

2%D

ied

of

vasc

ula

r d

isea

seA

nis

opoi

kil

ocyt

osis

Pin

ker

ton

et

al.,

1990

[1

1]16

40/F

MD

S46

,XX

,t(1

;13)

[8]/

47,X

X,

1

14[4

]/46

,XX

[5]

127

Ali

ve a

t 12

1

mon

ths

An

isop

oiki

locy

tosi

s,

oval

ocyt

es p

rese

nt

RA

EB

14%

AM

L46

,XX

,t(1

;13)

[21]

/47,

XX

,

1

14[2

]/46

,XX

[1]

M1

MD

S47

,XX

,

1

14[1

2]/4

6,X

X[3

3]A

llo

46,X

YB

MT

1767

/NA

MD

S47

,

1

1414

1N

AN

AE

stey

et

al.,

1991

[12

]C

MM

oLN

A

(con

tin

ued

)


149

Tab

le 2

con

tin

ued

No.

Age

(yea

rs)/

sex

Dia

gnos

isK

aryo

typ

eP

late

lets

10

3

/mm

3

an

d m

onoc

ytes

[%

]S

urv

ival

Red

cel

l m

orp

hol

ogy

Ref

eren

ce

1877

/MM

DS

45,X

,

2

Y,i

(14q

)42

2 m

onth

sN

AR

iber

a et

al.

, 199

1

[13]

CM

MoL

14%

1967

/MM

DS

45,X

,

2

Y,i

(14q

)[20

]31

3A

live

at

37 m

onth

sN

AS

ole

et a

l., 1

991

[14

]

RA

NA

2056

/MM

DS

47,X

Y,

1

14[9

0%]/

46,X

Y[1

0%]

190

AM

L a

t 73

mon

ths,

die

d

at 7

5 m

onth

sN

AB

riza

rd e

t al

., 19

92 [

15]

RA

RS

AM

L47

,XY

,

1

14[9

0%]/

46,X

Y[1

0%]

BM

stu

dy

not

don

e8%

2181

/MM

DS

47,X

Y,

1

14[5

]/46

,XY

[22]

140

6 m

onth

s la

ter,

die

d o

f ca

chex

iaN

AR

AE

B[T

wo

late

r st

ud

ies

wit

h 3

5% a

nd

17%

1

14]

7%22

63/M

MD

S47

,XY

,

1

14[6

]/31

7A

live

at

48 m

onth

sN

AR

A46

,XY

[29]

2%23

4/M

AA

47,X

Y,

1

14[1

2]/4

6,X

Y[2

]22

15 m

onth

sA

nis

opoi

kilo

cyto

sis

En

do

et a

l., 1

992

[16]

18M

DS

47,X

Y,

1

14[1

7]/4

6,X

Y[1

2]N

AR

AE

BT

2460

/MM

DS

46,X

Y,i

(14q

)[19

]/46

,XY

[1]

601

NA

NA

Liu

et

al.,

1992

[17

]

RA

EB

12%

CM

MoL

2574

/MM

DS

47,X

Y,

1

14[1

8]/4

6,X

Y[2

]60

NA

Red

cel

l ab

nor

mal

itie

sT

um

ewu

an

d R

oyle

, 19

92 [

18]

CM

MoL

2668

/FM

DS

46,X

X,i

(14q

)[6]

/46,

XX

[9]

282

Ali

ve a

t 42

1

mon

ths

NA

Man

cin

i et a

l., 1

993

[19]

RA

NA

2762

/MM

DS

47,X

Y,1

14[5

]/46

,XY

[15]

104

7 m

onth

sN

AR

AE

B47

,XY

,114

[3]/

46,X

Y,d

el(2

0)(q

13)[

8]/

12%

AM

L46

,XY

[4]

M2

CR

46,X

Y,d

el(2

0)(q

13)[

16]/

46,X

Y[6

]28

63/F

AM

L47

,XX

,114

[6]/

46,

XX

[9]

329

26 m

onth

sN

AM

2N

A29

88/F

MD

S47

,XX

,114

[16]

/46,

XX

[24]

209

NA

NA

Arr

anz

et a

l., 1

994

[20]

RA

RS

nor

mal

3070

/FA

ML

46,X

X,i

(14)

(q10

)[24

]/46

,XX

[3]

187

9 m

onth

sN

AP

oire

l et

al.

, 199

5 [2

1]M

2N

A

3152

/MA

ML

47,X

Y,1

14[2

9]/4

6,X

Y[9

]49

Die

d o

f lu

ng

infe

ctio

nN

AM

2N

A32

29/M

AA

47,X

Y,1

14[2

]/46

,XY

[29]

29A

live

at

1 ye

arN

AC

R46

,XY

NA

3364

/FA

ML

47,X

X,1

14/4

8,X

X,1

13,1

1471

18 m

onth

sN

AT

oze

et a

l., 1

997

[22]

M2

13%

Rel

apse

(1-y

ear)

47,X

X,1

14/4

8,X

X,1

13,1

14/4

8,X

X,1

14,1

21/

46,X

X34

76/M

AM

L47

,XY

,114

/48,

XY

,12,

114

/46,

XY

795

NA

15 m

onth

s; d

ied

of

sep

sis

Mar

ked

poi

kilo

cyto

sis,

el

lip

tocy

tes,

tea

r-d

rop

cel

ls

(con

tin

ued

)

150 K. S. ReddyT

able

2co

nti

nu

ed

No.

Age

(yea

rs)/

sex

Dia

gnos

isK

aryo

typ

eP

late

lets

103 /m

m3

and

mon

ocyt

es [

%]

Su

rviv

alR

ed c

ell

mor

ph

olog

yR

efer

ence

3566

/MM

DS

47,X

Y,1

14[8

]/46

,XY

[5]

175

8 m

onth

s, d

ied

of

mes

entr

ic h

emor

rhag

eN

AR

AE

BT

NA

3689

/FA

ML

47,X

X,1

14[1

3]/4

6,X

X[6

]45

1 m

onth

Ell

ipto

cyto

sis

M4

or M

5N

A37

72/F

MD

S47

,XX

,114

[14]

/46,

XX

[9]

.20

0N

AN

AR

AE

BT

NA

3830

/FM

DS

47,X

X,1

14[7

]/46

,XX

[11]

131

6 m

onth

sN

AR

AE

BT

NA

CR

(4

mon

ths)

3975

/MM

DS

i(14

q)36

2 m

onth

sN

AC

MM

oL43

%40

81/M

MD

SR

A46

,XY

,i(1

4)(q

10)[

15]/

46,X

Y[3

5]14

914

%A

live

at

10 m

onth

sM

any

elli

pto

cyte

s an

d

sch

isto

cyte

sB

oavi

da

et a

l., 1

997

[23]

Bol

dfa

ce t

ype

ind

icat

es c

ases

wit

h i

soch

rom

osom

e 14

q.

Abb

revi

atio

ns:

M,

mal

e; F

, fe

mal

e; M

DS

, m

yelo

dys

pla

stic

syn

dro

me;

AA

, ap

last

ic a

nem

ia;

RA

, re

frac

tory

an

emia

; R

AR

S,

refr

acto

ry a

nem

ia w

ith

sid

erob

last

s; R

AE

BT

, re

frac

tory

an

emia

wit

h e

xces

s of

bla

sttr

ansf

orm

atio

n;

PH

-ve,

Ph

ilad

elp

hia

ch

rom

osom

e n

egat

ive;

BM

T,

bon

e m

arro

w t

ran

spla

nt;

CM

Mol

, ch

ron

ic m

yelo

mon

ocyt

ic l

euke

mia

; M

PD

, m

yelo

pro

life

rati

ve d

isor

der

; aC

ML

, at

ypic

al c

hro

nic

mye

loid

leu

kem

ia; C

R, c

omp

lete

rem

issi

on; A

ML

, acu

te m

yelo

id l

euke

mia

(M

1/M

2 ar

e su

bgro

up

s); N

A, n

ot a

vail

able

.

tosis, and eight had no apparent medical history signifi-cant to aberrant red cell morphology. Although the totalnumber of cases examined is small, the data suggest thatthe aberrant red cell morphology may be a hematologicalfeature associated with trisomy 14 myeloid disorder.

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Trisomy 14 and Leukemia