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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.
The complete blood count was white blood cells, 29,900/mm
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.
Trisomy 14 and Leukemia
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.
The complete blood count was white blood cells, 32,000/mm
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.
The complete blood count was white blood cells, 30,700/mm
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].
Trisomy 14 and Leukemia
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
)
Trisomy 14 and Leukemia
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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