[CANCER RESEARCH 42, 2918-2929, July 1982]
0008-5472/82/0042-0000$02.00
Correlation of Karyotype with Clinical Features in Acute Lymphoblastic
Leukemia1
Yasuhiko
Kaneko,2 Janet D. Rowley,3 Daina Variakojis,
Robert R. Chilcote,
Irene Check, and
Masaharu Sakurai
Departments of Medicine [Y. K., J. D. R.I, Pathology [D. V.. I. C.], and Pediatrics [R. R. C.], and The Franklin McLean Memorial Institute ¡J.D. R.], The University of
Chicago, Chicago, Illinois 60637, and Division of Clinical Laboratories, Sa/fama Cancer, Ina, Sa/fama 362, Japan [M. S.]
ABSTRACT
We studied the clinical and karyotypic features of 50 patients
with acute lymphoblastic leukemia, including 33 American and
17 Japanese patients, at two institutions. Clonal chromosome
abnormalities were found in 39 of the 50 patients (78%) at
diagnosis. Eleven patients had diploidy (N patients). Among
the 39 aneuploid patients, 17 had pseudodiploidy (A1 patients),
eight had hyperdiploidy with 47 to 49 chromosomes (A2 pa
tients), nine had hyperdiploidy with 50 to 59 chromosomes (A3
patients), and five had other chromosome abnormalities. Of 14
patients whose chromosomes were also studied at relapse,
eight had karyotypic progression, five had abnormalities iden
tical or similar to those observed at diagnosis, and one had a
change of karyotype from diploidy to aneuploidy. The median
age and the median white blood cell count (WBC) of A3 patients
were lower than those of any other group of patients, and all
A3 patients had non-T-cell non-B-cell markers. The median
age and the median WBC of A1 patients were higher than those
of any other group of patients, although one-third of the patients
had WBC below 20 x 103/jul, and they often had leukemic
cells of T-cell or B-cell lineage. The A2 patients were relatively
old and tended to have higher WBC. The N patients were
relatively young and tended to have low WBC, although these
tendencies were not as marked as those in A3 patients. The
A3 patients had longer survival times than the A1 (p = 0.003)
or A2 (p = 0.002) patients. Also, N patients had longer survival
times than A1 (p = 0.03) or A2 (p = 0.05) patients. The
difference in survival times between A3 and N patients was not
significant.
Our study demonstrated that the karyotype is correlated with
survival and with other recognized prognostic factors. How
ever, in some A1 and A2 patients, the karyotype was a more
reliable factor in indicating a poor prognosis than was the WBC
or age.
INTRODUCTION
The chromosome
pattern in AN.LL" has been studied exten
sively with banding techniques (36), and the diagnostic as well
Received July 6, 1981; accepted April 1, 1982.
' This work was supported in part by United States Department of Energy
Contract DE-ACO2-80EV10360.
USPHS Grant CA-19266 awarded by the Na
tional Cancer Institute, Department of Health and Human Services, and The
University of Chicago Cancer Research Foundation.
1 Present address: Saitama Cancer Center. Ina, Saitama-Ken, 362 Japan.
3 To whom requests for reprints should be addressed, at Department of
Medicine, Box 420, The University of Chicago, 950 East 59th Street, Chicago,
III. 60637.
' The abbreviations used are: ANLL, acute nonlymphocytic leukemia; ALL,
acute lymphoblastic leukemia; Ph', Philadelphia (chromosome); UCHC, Wyler
Children's Hospital, University of Chicago; SCC, Saitama Cancer Center; FAB,
French-American-British
2918
Cooperative
Group; CNS, central nervous system; N
as the prognostic significance of the karyotype has been well
documented (12, 13, 33, 39). Although there have been fewer
reports on the chromosomes in patients with ALL than on those
in patients with ANLL, several observations have been made in
ALL. (a) Clonal chromosome abnormalities occur in about onehalf of the patients with ALL (29, 44). (o) Hyperdiploidy is the
predominant type of aneuploidy (29, 44). (c) There is a lack of
agreement regarding the correlation of survival and the karyo
typic pattern, although hyperdiploid patients may have a better
prognosis than those with diploidy or other forms of aneuploidy
(37). (d) Patients with particular abnormalities, such as the
Philadelphia chromosome (7), a t(4q-;11q + ) (43), and a
t(8q - ;14q + ) (4), have specific clinical features, (e) Karyotypic
evolution appears to be common in ALL (29, 46).
We studied the clinical and karyotypic features of 33 con
secutive American patients and those of 17 consecutive Jap
anese patients at 2 institutions. We found that cytogenetic
patterns are clearly correlated with survival and with hematological and other clinical features.
MATERIALS
AND METHODS
Chromosomes from bone marrow, peripheral blood, and/or a lymph
node were studied in 33 of 36 consecutive American patients with ALL
who were admitted to UCHC between January 1973 and February
1981 and in 17 of 18 consecutive Japanese patients with ALL who
were admitted to SCC between February 1976 and April 1979. There
were 31 pediatrie patients (age, <15 years), including 20 males and
11 females, and 19 adult patients (age, >15 years), including 11 males
and 8 females. Initial bone marrow aspirates and peripheral blood
smears were available for review in all patients except one American
patient (Patient 26); these aspirates and smears were stained with
Wright-Giemsa. Initial bone core biopsies were available for review in
all American patients but one (Patient 17); bone core biopsies were
not performed in Japanese patients. These biopsies were stained with
hematoxylin and eosin; stains for reticulin and iron were also carried
out. The diagnosis of ALL was made on the basis of FAB classification
(3). Immunological markers of leukemic cells were evaluated in 41
patients by means of erythrocyte rosette and erythrocyte + antibody
+ complement rosette formation and surface immunoglobulin deter
mination (21); ALL-associated antigen (17) and/or intracytoplasmic
IgM (21) were studied in some patients. Clinical data were recorded
for each patient at diagnosis; these included age, sex, presence or
absence of an anterior superior mediastinal mass, as well as CNS
involvement, hemoglobin, WBC with percentage of blasts, and platelet
counts. The initial induction therapy for the American children was
carried out according to Children's Cancer Study Group Protocols 141
patients, patients with diploidy: A1 patients, patients with pseudodiploidy; A2
patients, patients with hyperdiploidy with 47 to 49 chromosomes; A3 patients,
patients with hyperdiploidy with 50 to 59 chromosomes; NN patients, patients
having only normal metaphase cells in the bone marrow; AN patients, patients
having both abnormal and normal metaphase cells in the bone marrow; AA
patients, patients having only abnormal metaphase cells in the bone marrow.
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Karyotype and Clinical Features in ALL
(25), 161, 162, and 163 and for the Japanese children essentially
according to Protocol 6801 of Acute Leukemia Group B (16) with CNS
prophylaxis. Adults, both American and Japanese, were treated with
regimens including anthracyclines,
vincristine, and corticosteroids,
with or without CNS prophylaxis. Response to initial induction therapy
was designated as complete remission, partial remission, or no re
sponse; the occurrence of a relapse was shown, and the survival of
each patient was recorded in days on March 31, 1981.
A cytogenetic sample was obtained from all 50 patients at diagnosis
and from 14 patients also at relapse. Bone marrow cells were prepared
with direct and/or 24-hr culture techniques, and peripheral blood cells
were prepared by 24-hr culture without phytohemagglutinin. The lymph
node cells of Patient 41 were prepared with a direct technique. Chro
mosomes were analyzed with regular Giemsa stain and with Q- and/or
G-banding (35) methods; R- and C-banding methods (32, 40) were
also used in some cases.
We define abnormal clones as 2 or more metaphase cells with
identical extra chromosomes, 2 or more metaphase cells with identical
structural rearrangements, or 3 or more metaphase cells with identical
missing chromosomes. Karyotypes were described according to the
International System for Human Cytogenetic Nomenclature (1978) (2).
Marker chromosomes of totally unidentified origin were designated
according to the system devised by Sakurai and Sandberg (34); the
size of the chromosome and then its centromeric position are given in
parentheses following the word 'mar." The centromeric position was
designated according to the system proposed by Levan er al. (23), in
which M, m, sm, st, t, and T stand, respectively, for median point,
median portion, submedian portion, subterminal portion, terminal por
tion, and terminal point. For example, mar(C6,m) indicates that the
marker was a C6-sized chromosome and the centromere was in the
median portion.
A statistical analysis correlating the karyotype with patient survival
was performed according to the generalized Wilcoxon test (8). The
patients were classified on the basis of karyotype into N, A1, A2, and
A3 patients. The patients were also classified in 3 groups on the basis
of the frequency of abnormal mitotic cells in the bone marrow into NN
(the patients with nonclonal abnormalities were included in this group),
AN and AA patients, according to the method of Sakurai and Sandberg
(33). To confirm the independence of karyotype as a prognostic
variable, we used the Cox model with days in first remission as the end
point.
Chromosome and clinical findings for 12 of the 33 patients from
UCHC were published previously (11 ). However, in 4 of them, Patients
20 (J. J.), 24 (J. L.), 30 (K. G.), and 33 (M. L.), further chromosome
analyses provided new information, and the clinical information has
been updated for all 12 patients. The chromosome and some clinical
findings of the 17 patients from SCC will be published elsewhere (19).
RESULTS
The clinical data for all patients are summarized in Table 1.
Chromosomes of 30 of the 33 American patients were suc
cessfully examined with banding; in the remaining 3 patients
(Patients 29, 33, and 37), clonal abnormalities were identified,
but banding was unsatisfactory. Chromosomes of 9 of the 17
Japanese patients were examined with banding at diagnosis.
In the remaining 8 patients, chromosomes were studied only
with regular Giemsa staining at diagnosis; however, clonal
abnormalities were identified in all 8 patients. In 3 of these 8
patients, banding was used at the time of relapse. Clonal
chromosome abnormalities were found in 39 of the 50 patients
with ALL (78%) at diagnosis, including 23 of the 33 American
and 16 of the 17 Japanese patients. There were 11 N patients,
including 3 patients (Patients 1, 7, and 8) with nonclonal
abnormalities caused by structural rearrangements. Among the
39 patients with abnormalities, 17 were A1 patients, 8 were A2
patients, 9 were A3 patients, and 5 had other forms of aneuploidy including one case of near-haploidy, one case of hypodiploidy, and 3 cases of near-tetraploidy. There were too few
of the latter patients to make valid comparisons with the other
groups, and no conclusion can be drawn with regard to the
clinical correlations of this heterogeneous category.
Karyotypic and Clinical Features of Each Group
N Patients. The median age of the 11 N patients was 12
years. The median WBC was 9800//tl. The L1 and L2 subtypes
in the FAB classification were equally distributed among these
patients. None had a mediastinal mass. Immunological markers
were tested in 10 of these patients; 8 of them had non-T-cell
non-B-cell ALL, and the other 2 (Patients 5 and 8) had T-cell
ALL. One of the latter (Patient 8) had CNS and testicular
involvement and did not respond to various chemotherapy
regimens; he died 2 months after diagnosis. Chromosomes
obtained only from peripheral blood cells of this patient were
examined, and 2 cells with different nonclonal abnormalities
were noted. Patient 6 had a CNS relapse after 21 months in
complete remission; however, remission of both bone marrow
and CNS has been maintained for more than 28 months after
treatment for CNS leukemia. Patient 9 had a bone marrow
relapse after a complete remission and died. Eight other pa
tients continue in first remission. Among them, 2 adults, aged
25 and 48 years, are long survivors (Patient 10, 1551 + days;
Patient 11, 2545+ days).
A1 Patients. The karyotypes of the 13 patients from UCHC
are summarized in Table 2. About one-half of the aneuploid patients belonged to this group. In 6 of the total of
17 A1 patients, the sole abnormality was a simple reciprocal
translocation,
namely, t(1q —;19q + ) (Patient 13) (Fig. 1),
t(11q-;14p+)
(Patient 15) (Fig. 2), t(2p-;8q + ) (Patient 21),
t(16p+;17q-)
(Patient 22) (Fig. 3), t(12p + ;1 7q-) (Patient
24), or t(21q + ;22q-)
(Patient 26). One patient with
t(8q-;14q + ) (Patient 17) and one with t(5q-;8q + ;14q + )
(Patient 27) (Fig. 4) had additional abnormalities. The karyo
types were different in Patients 17,21, and 27, but an abnormal
chromosome 8 with a breakpoint at band 8q24 was observed
in all 3. The abnormal chromosome 8 was involved with a
different donor chromosome in each patient; however, in 2
(Patients 17 and 27) of them, the terminal segment of 8q was
translocated to chromosome 14, resulting in a 14q + chromo
some. A derivative chromosome consisting of chromosomes 1
and 11, resulting in partial trisomy of chromosome
1
(q12-qter),
was the sole abnormality in one patient (Patient
16). In 8 other patients, the abnormality was characterized by
partial deletions; a partial deletion of 9p, del(9)(p21 or p22),
was seen in 4 of them; a partial deletion of 7p, del(7)(p15), in
3; a partial deletion of 6q, del(6)(q21 or q23), in 2; a partial
deletion of 11 q, del(11 )(q13 or q21 ), in 2; and a partial deletion
of 2q, 8q, 12q, and 20p each in one. The median age of the 17
patients was 20 years. A mediastinaj mass was present in 4
patients and CNS involvement in one patient. The median WBC
was 44,600//il. The leukemic cells in 7 patients were of the L1
subtype, those in another 9 were of the L1-L2 or L2 subtype,
and those in the patient with t(2p —;8q+) were of the L3
subtype. Patient 17, with t(8q-;14q + ), had the L1 subtype at
diagnosis but had the L3 subtype at relapse, and Patient 27,
with t(5q —;8q + ;14q + ), had the L2 subtype. Immunological
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2919
y. Kanaka et al.
Table 1
Clinical, cytologìcal,and pathological data on 50 patients with ALL
diasin-tinal CMS
103//J)6915931190167305202018129142524724703039815120321176632271122241418832340105408303262
Immunologicalmass
volve(yr)Sex3M3F4M7M9M12F13F14M15F25M48F3M3F4M4M4M10M12F15M18F20M22M30F36F39M42M60F68M4M6M12M13M15M19M33M51
clas 103/1*4.75.514.93.39.889.76.321.113.938.33.110.649.544.691.786.47.43.1232.024.59.777.094.47.849.85.0377.0136.0215.8267.035.78.217.615.020.42.6
totherapyCRCRCRCRCRCR-CNS
sificationL112LILIL1L2L1L2L2L1L2LIL1L1L2LIL1L1-L2L2L1-L2L3L2L2L1L2L1L2L2L1L1LILIL2L1L2L1-L2L1-L2L1L1L1L2L2L1L1-L2L2L2L2L2L1L224.
/dl)6.87.47.76.38.011.97.510.25.514.08.75.48.111.213.35.011.68.46.99.68.25.914.512.58.55.09.68.56.88.96.85.48.89.39.79.46.35.82.97.77
ment
markersN-T.
Patient8N
patients1234567891011A1
A+N-T,
N-B,
+N-T, N-B, A
N-BN-TT-CellN-T,
+1503
N-BN-T,
RCRNRCR-RCRCRCR-RCR-RCRCRCRCR-RC
+++ND—+ND————ND±——++ND+ND+
+356
++
N-B, A
+686031551
T-CellN-T,
N-BNTN-T,
+2545
N-BN-T,
+720
patients1213141516171819202122232425262728A2
N-BN-T,
N-B+
T-Cell+
T-CellN-TPre-B-cellN-T+
+829652
+42
+691
+991418
+27013356058169405671805
N-B+
N-T,
NTNTPre-B-cellN-T,
N-BN-T,
N-BN-T,
N-BNT+
+—ND———ND—ND+
B-CellN-T,
N-BN-T,
RNRCRCR-RCRPRCR-RCR-RCR-RNRCRCRC
+23286
patients2930313233343536A3
+N-T,N-B, A
N-BN-T,
+NTNT+
N-B, A
+420265
+10898311452106384
NTB-CellNTN-T.
++—NDND—NDNOND—NDNDNDND-NDrenort
+
F2M2M2F3F4M4F4FSM15F17F27F48M16M31M1
patients373839404142434445Patients
+N-T,N-B, A
N-BNTN-T,
+739
+1862
+1216
N-BN-TN-TN-TN-T,
+1460
+1611
RCRCRCRCR-RPRCR-RCRCR-R,
+1630
+881
N-BN-T,
+1384
N-BN-T,
+968507536106
otherabnormalities4647484950a
with
N-BN-T,
N-BN-T,
N-B+
Pre-T-cellcN-T,
+5871fi.
N-Bresnertivelv
Patients 6, 10,Age
36.1
1. 18. 20.FAB 26. 30.WBC(X
35.
oresent,23
40 inidentical28,
the
are 1fi,
to Patients fi 1.4.
antlrespectively,
14
7, 8, 9, 11, 13,Survival(days)184+532+599+110
?ñPlatelets(X
2 in the previous report from UCHC (11). Patients 9. 12%ofblasts22953124750207871204176482478133662296936083869697497760954222748821078440083635091HGB6(g
32, 34, 38, 39, 41Me42. 43, 45, 46. 47, 48, and 50 are identical,Response
to Patients 9. 3.
13, 15, 17, 7, 11, 2, 1, 5, 6. 4, 8, 10, 12, 16, and 14 in the previous report from SCC (19).
6 HGB. hemoglobin; BM, bone marrow; ND, not done; N-T. N-B, non-T-cell, non-B-cell; A, ALL-associated antigen; N-T, non-T-cell, B-cell marker was not tested;
NT, not tested; CR, complete remission; CNS R, CNS relapse; NR, no response; R, bone marrow relapse with or without CNS relapse; PR, partial remission.
c See results in the text.
markers of the leukemic cells were tested in 14 patients; 2 had
T-cell ALL, 2 had pre-B-cell ALL, one had B-cell ALL, and the
remaining 9 had non-T-cell non-B-cell ALL. Four patients,
including
one
with
t(2p-;8q + ) and
another
with
t(16p + ;17q-),
had no response to chemotherapy. Two pa
tients, one with t(21qt;22q-)
forming a Ph' chromosome and
2920
the other with 6q- and i(17q), had a partial remission. The
remaining 11 patients had a complete remission; however, 7 of
them had a relapse, and 5 of the 7 have died.
A2 Patients. The karyotypes of 6 A2 patients from UCHC
are summarized in Table 3; 8 patients belonged to this group.
Both structural and numerical abnormalities were seen; the
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Karyotype and Clinical Features in ALL
Table 2
Chromosome findings on 13 A1 patients from UCHC
Table 3
Chromosome findings on 9 A2 and A3 patients and one patient with nearfrom
UCHCNo.
ofcellsstudiedSource
ofcellsstudiedClinical
ClinicalPatient"
status13
D"R14
withcells
of
karyotypegPB banding
18
Representative
N(22%)/46.XX.«1:19)
Patient(q21;q13X78%)
patientsBM
A2
D15
29
N(10%)/46,XX,t(1;19),del
29(3Xq23),del(1
X90%)BM
1Xq21
N(9%)/46,XY.del(9)(p22),del(20Xp12X91%)BM
11
D16
30(q13;p13X24%)BM
17
D17
DR18
14X32%)BM,
PB
withstatus Source
karyotypeD6
of cells
N(76%)/46,XY,t(11;14)
25
N(68%)/46,XY,-11,+der(11)t(1;11Xq21;q
31
N(29%)/46,XY,-8,del(3)(q12q25),t(8;14Xq24;q32),+
banding
PB
10
N(60%)/47,XY.-16.-17,—
mar2.+
18, —
20. + mar! .+
mar4,+
mar3, +
mar5(40%)D
PB
25
N(68%)/47,XY,-10,-12,+
17,del(11Xp11).del(16)(q22),
der(10)t(10;7)(q22;?),
+
der(12)t(12;?)(q15;?)(16%)/48,same,+
+
mar1(G,tX16%)R
PB
2
der(8)t(1q;8qXcen;cen)(71%)PB
16
N(69%)/46.XY,-8,-13,del(3),t(8;14),+der(8)
31(1q;8q)t,+der(13)t(13;?)(q34;?X31%)BM
D19
14
DR20
12
(100)%D
BM
N(50%)/46,XX,del(9)(p21X50%)
(8%)D
N(37%)/46,XY,del(6Xq21
23).del(9Xp22),del(11Xq13X18%)/46,XY,del(6),del(7Xp1
or
PB
mar1(G,tX50%)R
BM
33PB
Representative
26
16
24
5),del(9),del(11X18%)/46,XY,-6,del(9),deld
i(6pX9%)/relatedkaryotypes(18%)BM
1), +
46,XY,-7,-10,-12,—
6),+der(10),
17. del(1 1),deld
i(17q),
+ der(12), +
+ marl
N(65%)/47,XY,-19,+
mar2(G,sm)(27%)/46,XY,-19,+
mar! (F,st), +
marl
N(50%)/47.XY,-C,+
18, +
N(33%)/46,XY,-2,-5,-6,-7,
-12,-16,
-9, -10, -11,
18,+der(2)t(2;?Xq35;?),
+ 8, +
der(11)t(1
+
,+ 1;?Xq21 ;?), + mar1
mar4.+
mar2, + mar3, +
mar5(4%)/karyotypicinstabilityD
6
N(66%)/46,XY,del(6),del(7),del(9),del(11X17%)/
3546,XY.-6.del(9).del(11),+
PB
39
N(5%)/49,XY,
12,-13,t(6;18Xp25;q21),t(11;14Xq23;q32),+
+ 7, +
i(6pX17%)BM
DR21
15
46,XX.del(7Xp15),del(9)(P22X1
14
46,XX,del(7),del(9X50%)/47,XX,del(7),del(9),+
der(9)t(9;?Xp24;?),+
der(13)t(1;13Xq12;p13)(31%)/50,XY,same,
20(24%)/related
+
00%)BM
clonesR
(F,tX7%)/relatedclonesPB
marl
BM
D22
N(53%)/46,XX,t(2;8)(p12-13;q24X47%)BM
43
D24
36(100%)BM
DR26
D27
atdiagnosisD
BM
14
46,XY,t(16;17Xp13;q23)
23
N(74%)/46,XX,t(12;17)(p13;q12X17%)/47,XX.t(1
patientsBM
2; 17). + mar! (C,smX9%)
37(p21),t(12;17X50%)PB
14
N(50%)/46,XX,del(9)
BM
15
N(53%)/50,XY,
B(?5),+
+
G(?21),+mar1(E.smX47%)D
C(?10), +
N(50%)/46,XY,t(21;22)(q22;q11X50%)
30
46,XX,-18,t(5;8;14)(q11;q24;q32),t(12;22)(p13;q11),
BM
32
+
N(53%)/58,XX
6,+
+ 4, +
14,+
7, + 10, +C, + 14, +
21.+del(18Xq21),+
mar1(C6,sm),+
mar2(E18,st),+mar3(G,tX47%)
18, 20,
and 26 in the present report are identical, respectively,
. and 9 in the previous report (11).
" ''
to patients 16, 17, 8,
R,AAltaNo.
D, diagnosis;
relapse; PB, peripheral blood; BM, bone marrow; N, normaltetraploidy
Near-tetraploidy
49
pattern of chromosome change varied from one patient to
another. Unidentified marker chromosomes were seen in 4
patients. Extra chromosomes 7,12,13,17,18,
and 19 were
each seen in one patient.
The median age was 14 years. One patient had CNS involve
ment, but none had a mediastinal mass. The median WBC was
19,000/fil. Leukemic cells in 2 patients were of the L2 subtype;
one of them had B-cell ALL. Six others had the L1 subtype;
immunological markers were tested in 3 of them, and all had
non-T-cell non-B-cell markers. One patient had no response to
chemotherapy, another had a partial remission, and the re-
N(12%)/48,XX,
13,+
+
19(69%)/47.XX,+
A3
14
der(18)t(18;?)(q23;?X100%)24.
16
19(19%)D
40BM
D"Patients
Analysis
unsatisfactorybut
was
similarabnormalities
showed
seen
D
BM
D
BM
20
56,XXY, + 4, + 6. + 10. + 15,
+ 17, + 18. + 21. + 21,
+ mar1(G,tX100%)
N(22%)/90,XXYY,-9,
-9, + 2minutes(78%)
Patients 30, 33, 35, 36, and 40 in the present report are identical, respec
tively, to patients 11, 13. 15, 14, and 12 in the previous report (11).
0 D, diagnosis; R, relapse; PB, peripheral blood; BM, bone marrow; N, normal
cells.
maining 6 achieved a complete remission; however, 4 of them
had a relapse and have died.
A3 Patients. The karyotypes of 3 patients from UCHC are
summarized in Table 3; 2 of these plus one patient from SCC
were the only 3 (Patients 38, 40, and 44) of the 9 patients in
this group who could be studied adequately with banding. The
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2921
Y. Kaneko et al.
karyotype of Patient 44 is presented in Fig. 5. Extra chromo
somes 4 and 6 were seen in all 3 patients, and extra chromo
somes 10 and 21 were seen in 2 of them. Patient 46, who had
a mosaic of cell lines with 28 and 56 chromosomes, had the
same chromosome changes, namely, +6, +10, and +21, in
the hyperdiploid cell line. There is, therefore, much more
consistency in the chromosome changes in these patients than
was noted in the A2 patients. The median age of the 9 patients
was 4 years; none had a mediastinal mass or CMS involvement.
Except in Patient 39, WBC were low; the median WBC was
4300//il. Non-T-cell non-B-cell markers were seen in the leukemic cells of all 8 patients who were tested. Four patients had
the L1 subtype and the other 5 had either the L1-L2 or L2
subtype. All patients but one (Patient 42) continue in a complete
remission (84+ days to 1862+ days); Patient 42 had a CNS
relapse but continues in bone marrow remission.
Karyotypic Evolution at Diagnosis and at Relapse
t(8q-;14q+).
Patient 35 had a 14q+
chromosome
with the
extra segment of the 14q+ chromosome translocated from
11q. Leukemic cells in the T-cell lineage were seen in 5
patients. T-Cell ALL was observed in 2 N patients (Patients 5
and 8) who had no mediastinal mass. Two others (Patients 14
and 15) with T-cell ALL were A1 patients and had a mediastinal
mass; one of them (Patient 14) had 9p— and 20p— and the
other (Patient 15) had t(11q-;14p+).
The results of immunological studies on Patient 49 (courtesy of Dr. John H. Kersey,
University of Minnesota) were: erythrocyte rosettes, 12%;
erythrocyte + antibody + complement rosettes, 2%; surface
IgG, 14%; T 101 antigen, 6%; T 9.6 antigen, 23%; and TA1
antigen, 57%. These data suggested that the leukemic cells
might be in an early stage of T-cell differentiation (pre-T-cell).
This patient had near-tetraploidy with missing No. 9 chromo
somes and had a mediastinal mass. Twenty-six patients had
non-T-cell non-B-cell markers in the leukemic cells, and the
remaining 6 patients had non-T-cell markers (B-cell markers
were not tested in these 6 patients); with one exception, none
of these 32 patients had a mediastinal mass. Patient 19 had a
mediastinal mass and non-T-cell non-B-cell ALL; he was not
tested for T-cell antigens. This patient had a 6q— and a 9p —
chromosome. Patient 20, who was not tested for immunological
markers, had a mediastinal mass, and a 7p- and a 9pchromosome. A 9p— (Patient 18), a 7p— (Patient 28), or a
6q—(Patient 25) chromosome each were seen in one patient,
whose leukemic cells had non-T-cell non-B-cell markers and
who had no mediastinal mass. All A3 patients, had non-T-cell
non-B-cell ALL, and none of these had a mediastinal mass.
We defined karyotypic evolution as 2 or more abnormal
karyotypes present at diagnosis which were related to each
other. Evolution of the karyotype was found in 11 of the 50
patients (22%); it appeared to be unrelated to prognosis.
Forty of the 50 patients (80%) achieved a complete remis
sion. Fifteen of the 40 patients had a bone marrow relapse
after a remission; all but 2 have died. Chromosomes were
studied in 14 patients at relapse; in 10 of these, banding
studies were adequate both at diagnosis and at relapse. New
leukemic clones derived from the clone seen at diagnosis were
observed in 8 patients, indicating karyotypic evolution; the
evolution associated with a relapse was termed karyotypic
Correlation of Karyotype with Survival
progression. Karyotypic progression seen in Patient 13 is
presented in Fig. 1. In Patient 9, the leukemic cells changed
We compared the survival times of N, A1, A2, and A3
their karyotype from diploidy to pseudodiploidy. Patient 19 had
patients. Five patients, including one with near-haploidy, one
identical abnormal karyotypes both at diagnosis and at relapse.
with hypodiploidy, and 3 with near-tetraploidy, were excluded
In the remaining 4 patients, the leukemic cells were confirmed
from evaluation because of the small number of patients in the
to have the initial chromosome abnormalities; however, the
subgroup with each abnormality. The actuarial survival of 11 N
difference in abnormalities at diagnosis and at relapse could
patients was 75% at 2545 days. The actuarial median survival
not be defined precisely because of the lack of analyzable
of 17 A1 patients was 674 days and that of 8 A2 patients was
cells, poor chromosome banding, or both.
458 days. All 9 A3 patients are alive (84+ to 1862+ days).
Among evolutionary changes in the 8 patients, structural
The difference in survival times in the 4 groups of patients was
rearrangements were seen in 7; a deletion of 1q, 3q, 9p, and
significant (p = 0.0016). The difference in survival times
11 q each was seen in one patient, a derivative chromosome of
between N and A1 patients and that between N and A2 patients
chromosomes 2, 11, and 13 each in one, an isochromosome
were significant (p = 0.03 and p = 0.05), but that between N
of 17q in one, and unidentified marker chromosomes in 3.
and A3 patients was not significant. The difference in survival
Numerical changes were seen in only 3 patients; one had —7,
times between A3 and A1 patients and that between A3 and
one had +2, and the other had +14. Of these 8 patients with
A2 patients were significant ( p = 0.003 and p = 0.002). When
karyotypic progression, 3 had an increase in the number of we compared the survival of N patients with that of abnormal
chromosomes, 3 had no numerical change, and the other 2 patients (A1, A2, and A3 patients), the difference was not
had a decrease in number.
significant. Actuarial survival curves of N, A1, A2, and A3
patients are presented in Chart 1.
Correlation of Karyotype with Immunological Markers
We also compared survival times between NN, AN, and AA
patients. Thirteen of the 50 patients were excluded from eval
Immunological markers were examined in the leukemic cells
of 41 of the 50 patients. Leukemic cells in the B-cell lineage
uation because chromosomes in the bone marrow cells had not
been studied. Nine were NN patients, 22 were AN patients,
were seen in 4 patients, all of whom had a clonal abnormality.
Two of them had a pre-B-cell phenotype, which is characterized
and 6 were AA patients. The actuarial survival of NN patients
by the presence of intracytoplasmic IgM and the absence of was 82% at 2545 days. The actuarial median survival of AN
patients was 1026 days and that of AA patients was 418 days.
surface immunoglobulin. Both were A1 patients; Patient 17 had
t(8q-;14q + )and Patient 22 had t(16p+;17q-).
Two patients
The difference in the survival times for the 3 groups of patients
was almost significant (p = 0.052). The difference in survival
had B-cell ALL. Patient 27 had t(5q-;8q + ;14q+); the break
times between NN and AN patients and that between AN and
points of 8q and 14q were the same as those in the usual
2922
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Karyotype and Clinical Features in ALL
AA patients was not significant, but that between NN and AA
patients was significant (p = 0.02). Actuarial survival curves
of NN, AN, and AA patients are presented in Chart 2.
Prognosis in ALL also depends on initial WBC, age, sex, and
FAB morphology. It is difficult to subgroup the patients by these
criteria using conventional analyses. To determine the inde
pendence of prognostic factors, we used the Cox model.
Bone Marrow Reticulin
Bone marrow reticulin was slightly to greatly increased in 11
of 32 American patients in their bone core biopsies (Table 1).
Among those 11 patients, 3 had the L1 subtype, 7 had the L1L2 or L2 subtype, and one had the L3 subtype. The 11 patients
IOO
90
80
70
60
P=OOI6
30
20
Hyperdiploidy(50-59l(n
=9)
Diploidy(n=ll)
Pseudodiploidy (n =l7)
Hyperdiploidy (47-49)(n =8)
IO
O O
300
600
900
1200
1500
I8OO
2100
2400
Days from Diagnosis
Chart 1. Actuarial survival curves of 11 N patients, 17 A1 patients, 8 A2
patients, and 11 A3 patients. The difference in the survival times in the 4 groups
of patients was significant (p = 0.0016).
lOOc
iL..iiiÕ
0L,
!AA
Patients(n=6)
P=.052l
i)
l
l
l
i
900
1200 1500 1800 2100 24
Days from Diagnosis
Chart 2. Actuarial survival curves of 9 NN patients, 22 AN patients, and 6 AA
patients. The difference in the survival times in the 3 groups of patients was
almost significant (p = 0.052).
300
i
600
DISCUSSION
Karyotypic Features in ALL. Our study demonstrated that
78% (39 of 50) of ALL patients had clonal chromosome ab
normalities at diagnosis; this incidence is higher than that noted
by previous investigators (29, 44). Although hyperdiploidy was
reported to be the predominant form of aneuploidy in ALL
patients (29, 44), the number of A1 patients and that of A2 and
A3 patients, were equal in our study. Hypodiploidy was seen in
only one patient. The higher incidence of clonal abnormalities
and of pseudodiploidy may be related to the fact that our group
included a relatively high percentage of adults (19 of 50). It is
also likely that, with banding, subtle abnormalities were de
tected in the leukemic cells of A1 patients whose karyotype
appeared to be diploid with regular Giemsa stain. The abnor
mality in A1 patients was rather simple; generally, it was
reciprocal translocation or a partial deletion. We observed a
deletion of 9p in 4 of our 17 A1 patients at diagnosis. A 9pchromosome was observed in another A1 patient (Patient 24)
as an evolutional change when she had a relapse. A translo
cation involving 9p was seen in one patient (Patient 35) at
diagnosis and was seen in another (Patient 9) at relapse, in
addition to other complex abnormalities. Abnormalities of 9p
have not been commented on in other studies (29, 44).
The abnormalities in hyperdiploid cells were usually compli
cated, and one-half of them had 4 or more extra chromosomes;
this is relatively rare in ANLL patients (20). There were no
identical abnormal karyotypes among our patients; this may
indicate that the karyotype in ALL is more heterogeneous than
that in ANLL, possibly reflecting the greater heterogeneity of
the lymphocyte population. Paradoxically, however, cells from
patients with 50 or more chromosomes showed some relatively
consistent additions, such as +4, +6, +10, +18, and/or
+21. Except in one patient with a +18, additions of these
chromosomes were not observed in A2 patients. The A2 and
A3 patients are thus chromosomally distinct, and the chromo
some pattern of the A3 patients may be associated with their
unusually "low-risk" clinical course.
The occurrence
of a complex
3-way translocation,
t(5q-;8q + ;14q + ), in Patient 27 with B-cell ALL is analogous
to that of complex Ph1 translocations in the patients with
70604020IO°<!>.
^S«90HO
were classified as N, A1, or A2 patients; none of them were A3
patients. Of the 11 patients, 4 had no remission, one had a
partial remission, and 6 had a complete remission; 4 of the 6
had a relapse.
chronic myelogenous leukemia (15); in the chronic myelogenous leukemia patients, 2 of the chromosomes involved were
chromosomes 9 and 22 with breaks in the usual band. A similar
occurrence of 3-way translocations has been reported in some
patients with acute myeloblastic leukemia (FAB subtype M2)
(24) (in these patients, 2 of the 3 chromosomes were chro
mosomes 8 and 21) and in some patients with acute promyelocytic leukemia (FAB subtype M3) (6) (in these patients, 2 of
the 3 chromosomes were chromosomes 15 and 17). Our case
appears to be the first report describing a 3-way translocation
involving the No. 8 and 14 chromosomes.
Because of the difficulty of obtaining adequately banded
chromosomes, reports describing the banding pattern have
been fewer for ALL than for ANLL. Remarkable improvements
have been obtained in recent years, however, and several
JULY 1982
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2923
Y. Kaneko et al.
specific changes have been reported; these include a Ph1
chromosome (7), t(8q-;14q + ) (4), a 14q+ chromosome that
was not involved in a translocation with the terminal segment
of 8q (11, 29), t(4q - ;11 q + ) (43), a partial deletion of 6q (29),
near-haploidy (9, 22), and hyperdiploidy with many extra chro
mosomes (19). We had no patients with t(4q —;11q+), whereas
this observed in 4 of 52 ALL patients of Van den Berghe ef al.
(43), 4 of 34 patients of Prigogina et al. (30), and one of 31
patients of Oshimura ef al. (29).
Evolution of Karyotype in ALL. Evolution of the karyotype
at diagnosis as evidenced by the presence of 2 or more
abnormal karyotypes that are related to each other seems to
be more common in ALL patients than in ANLL patients. We
found it in 11 of the 50 ALL patients, and Hagemeijer ef al.
(14) noted it in only 10 of 86 ANLL patients. The clinical
significance of a mosaic karyotypic pattern at diagnosis is
uncertain at present.
Karyotypic progression was seen in most patients whose
chromosomes were adequately studied with banding both at
diagnosis and at relapse. In our previous paper on the chro
mosome pattern in 16 patients with ALL (11), the leukemic
cells of 3 patients, Patient 20 (J. J.), Patient 24 (J. L.), and R.
J., were reported to have changed their karyotype from diploidy
at diagnosis to aneuploidy at relapse. In one patient, Patient
20 (J. J.), deletions of 7p and 9p were detected in the pretreat
ment sample on further analysis; these deletions had been
overlooked initially because of the subtle nature of the abnor
malities and the poor quality of the banding. In another patient,
Patient 24 (J. L.), only normal cells were analyzed initially;
analysis of another 23 cells showed that 6 cells had a consist
ent abnormality. Because only one cell of the other patient (R.
J.) was examined at diagnosis, this patient should be excluded
from evaluation. Among 23 American patients with abnormali
ties in the present study, 12 had 50% or fewer aneuploid cells
in their bone marrow or peripheral blood samples at diagnosis.
The presence of presumably nonleukemic dividing cells has
been reported in the blood of leukemic patients (18); most of
them were children with ALL, and all were in relapse or remis
sion. Thus, the presence of many diploid presumably nonleu
kemic dividing cells, either in the blood or in the bone marrow
and either at diagnosis or at relapse, may cause errors in
chromosome analysis of ALL. In this larger series, a change of
karyotype from diploidy to aneuploidy was seen in only one
patient (Patient 9); the possibility that we studied only normal
dividing cells in her initial bone marrow sample cannot be
excluded.
The evolutionary changes in our ALL patients were mainly
structural and were quite variable. This pattern was markedly
different from that reported in ANLL patients (41); the most
frequent evolutionary change in ANLL was the gain of one or
more chromosomes, most often +8 and/or +18.
We observed that, with one exception, all patients studied at
relapse had the abnormalities originally seen at diagnosis.
Moreover, karyotypic progression was identified in one-half of
these patients. Zeulzer ef al. (46) reported similar results in a
series studied prior to banding; they found karyotypic evolution
in 31 of 71 children (44%) with acute leukemia, which occurred
during relapse in most cases. In the great majority of these 31
patients, some features of the original karyotype were observed
in the leukemic cells at relapse.
Whang-Peng ef al. (44) studied karyotypes in 153 ALL
2924
patients at diagnosis, mainly on the basis of nonbanded chro
mosomes. New aneuploid clones developed in 24 of these
patients at relapse. The new clones were similar to those
originally present in 12 of the 24 patients; in the other 12
patients, however, entirely new clones developed. SeekerWalker ef al. (38) studied chromosomes in 25 ALL patients at
diagnosis; in 9 of these, chromosomes were also studied at
relapse. Among the 9 patients, 3 had abnormal karyotypes
similar to those seen at diagnosis; however, the other 6 had
chromosome features that were distinctly different from those
observed at diagnosis. The authors suggested that, in a sub
stantial number of ALL patients, malignant transformation of
previously unaffected cells occurred after total eradication of
the original clone. In contrast to their findings, our observations
on the chromosome pattern in the same patients at diagnosis
and at relapse demonstrate the appearance of a new leukemic
clone derived from the original clone, rather than the emer
gence of an independent clone. These data support the sug
gestion by Kaneko ef al. (19) that the original abnormal clone
is substantially reduced by chemotherapy, and as a result the
patients enter remission. A relapse occurs when the original
surviving leukemic cells have developed the capacity to prolif
erate more rapidly or to resist chemotherapy. Such a modifi
cation may be related to progression of the karyotype.
Correlation of Karyotype with Immunological
Markers. It
has been reported that most karyotypes in B-cell ALL included
either a 14q+ chromosome that was not involved in a translo
cation with 8q (11, 29) or t(8q-;14q + ) (4) which was appar
ently identical to the translocation observed in most patients
with Burkitt lymphoma (45). Karyotypic and immunological
studies on the leukemic cells of Patient 17 indicated that the
cells with t(8q-;14q + ) can be seen not only in B-cell ALL but
also in pre-B-cell ALL (21). Recently, variant translocations
have been reported in Burkitt lymphoma; these include
t(2;8)(p12-13;q24)
(26) and t(8;22)(q24;q11 ) (5). Patient 21,
whose leukemic cells had t(2p—;8q + ) and were of the L3
subtype, may have had leukemic cells in the B-cell lineage, but
immunological studies were not performed (31). An abnormal
chromosome 8 in the 3 patients with leukemic cells of B-cell
lineage or of the L3 subtype had the same breakpoint, namely,
8q24, although the abnormal chromosome 8 in each patient
was involved with different donor chromosomes. This finding
suggests that breakage in chromosome 8 at band q24 may be
the critical event in malignant transformation or in providing Bcells with a selective advantage. The leukemic cells of Patient
22 had t(16p + ;17q—) and a pre-B-cell phenotype. Further
studies were required to clarify whether certain specific kary
otype patterns are associated with pre-B-cell (21).
Two of the 5 patients with a mediastinal mass had T-cell ALL.
In another one of the 5, leukemic cells might be in T-cell
differentiation on the basis of various antigen studies. It is
possible that another patient with a mediastinal mass, in whom
non-T-cell non-B-cell ALL was diagnosed on the basis of neg
ative erythrocyte rosettes and negative surface immunoglobulin, could have been found to have cells of T-cell lineage if the
appropriate antigens had been used. Abnormalities of chro
mosome 9 were seen in 4 of the 7 patients with T-cell markers
and/or a mediastinal mass; these abnormalities included 9p—
(Patients 14, 19, and 20) and -9 (Patient 49). A 6q- chro
mosome was seen in one patient (Patient 19) with a mediastinal
mass. There have been few reports on chromosome studies on
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Karyotype and Clinical Features in ALL
T-cell ALL. A 6q-
(29), a 5q-
and a 9p-
(1), and a 14q +
chromosome (27) each were reported in one patient. The
findings from our data and from others suggest that chromo
somes 9 and 6 may frequently be involved in rearrangements
in ALL of T-cell lineage, although they may also be seen in ALL
with another immunological phenotype. Among 7 patients with
T-cell markers and/or a mediastinal mass, 4 were A1 patients.
Three of the 4 patients with leukemic cells in the B-cell lineage
were also A1 patients. Thus, T-cell or B-cell markers appear to
be seen frequently in A1 patients.
The karyotypes in patients with non-T-cell non-B-cell ALL
were heterogeneous; however, all of the A3 patients had this
immunological phenotype, suggesting that this group of pa
tients may have homogeneous immunological markers.
Prognostic Implications of the Karyotype in ALL. The chro
mosome subgroups that we have defined show a very good
correlation with other previously identified prognostic features
except for FAB subtypes; these are summarized in Table 4.
We separated the patients with hyperdiploidy into 2 groups
consisting of A2 and A3 patients because the study of Kaneko
ef al. (19) suggested that the latter group had a favorable
prognosis. In the present study, we have identified a difference
in the pattern of extra chromosomes in these 2 groups provid
ing further support for the notion that the A2 patients and the
A3 patients belong to different subgroups. It has been well
documented that the patients between the ages of 3 and 7
years who have WBC below 10,000//tl (25) and non-T-cell
non-B-cell markers (10) are expected to have the best prog
nosis of all the ALL patients. Interestingly, most of our A3
patients had all of the above factors. The N patients tend to
have low WBC and seem to be young, although these tenden
cies are not as marked as those in the A3 patients. The A1 or
A2 patients were older and had higher median WBC than the
N or A3 patients. They had T-cell or B-cell ALL more frequently
than did the N or A3 patients. All of these findings are consid
ered poor prognostic signs. However, WBC were low in onethird of the A1 or A2 patients; these had no response to
chemotherapy or had a relapse after a complete remission,
and most of them died. In these patients, the karyotype was a
more reliable factor indicating poor prognosis than were the
WBC. We also used the Cox model to judge the independence
of karyotype as a prognostic variable and found that, after
Table 4
Correlation of chromosome subgroup with favorable prognostic factors and with
survival
No. of patients
cell
non-B-cellmarkers8a/
Xio3/M"6526WBC
<20X10V/1I8648Non-T-
patientsA1
N
IO69d/143^48/8FABU6754Alive9
2545daysc)6
(75% at
patientsA2
patientsA3
patientsTotal111789AgeS7yr4528WBC
days82
674
days89
458
One patient was tested only for T-cell marker.
The denominator indicates the number of patients who were tested for
immunological markers.
Actuarial survival.
Two patients were tested only for T-cell marker.
8 Actuarial median survival.
Three patients were tested only for T-cell marker.
JULY
WBC and age, karyotype was still a significant and predictive
variable (p< 0.01).
We could not analyze the difference in survival between
near-haploid patients and those with other abnormalities, be
cause only one patient had this abnormality. The patient re
lapsed after 16 months in complete remission, and her survival
was 31 months. Recently, Brodeur ef al. (9) summarized the
clinical features of 6 patients with near-haploidy, including 2 of
their patients and 4 others published previously. The median
survival of the 6 patients was only 10 months. They stated that
near-haploid ALL may represent a special subgroup of ALL
with a poor prognosis.
It has been reported that the patients with the L1 subtype
survived longer than did those with the L2 or L1-L2 subtype
(25). In contrast to the good correlation of the karyotype with
other previously identified prognostic factors, our study
showed no correlation between the chromosome subgroup and
the FAB subtype (Table 4). It appears from this small series
that the increased reticulin in bone marrow may be another
factor associated with poor prognosis; thus, of the 11 patients
with increased reticulin, only 4 are still surviving. This finding
needs to be confirmed in other series at other institutions.
None of the A3 patients had increased reticulin.
Previous series of patients have been classified into different
groups from the ones we have used, and thus our results
cannot be compared directly. Since some patients with abnor
malities have a favorable prognosis while others have a poor
prognosis, combining all patients with abnormalities obscures
these differences. Although it is not surprising that, in a study
of 331 ALL patients, Whang-Peng ef al. (44) concluded that
there was no prognostic difference between the patients with
diploidy and those with aneuploidy, Seeker-Walker ef al. (37)
reported that children with hyperdiploidy had a better prognosis
than those with diploidy, pseudodiploidy, or hypodiploidy; there
was, however no prognostic difference between the patients
with diploidy and those with aneuploidy.
The data from the Third International Workshop on Chro
mosomes in Leukemia (42) showed that patients with 51 to 60
chromosomes and those with diploidy had a longer survival
than those with pseudodiploidy. Adult patients with 47 to 50
chromosomes had a shorter survival; however, children in this
group had a longer survival. This result is very similar to ours,
except that our A2 patients, including children as well as adults,
had a poor prognosis.
Sakurai and Sandberg (33) observed that AA patients with
ANLL (primarily adults) had very short survival times compared
with AN or NN patients. This observation was confirmed with
banding studies by several other investigators (12, 13, 28). Of
37 patients whose bone marrows we studied, the NN patients
had a longer survival than the AA patients. However, there was
no difference in survival either between NN and AN patients or
between AN and AA patients. The Third International Workshop
on Chromosomes in Leukemia (42) reported that, among adult
ALL patients, NN patients had a longer survival than did AN or
AA patients. There was, however, no difference between the
survival of AN patients and that of AA patients. Among patients
with childhood ALL, there was no difference in survival times
for NN, AN, and AA patients. Our data and those of the Third
International Workshop on Chromosomes in Leukemia sug
gested that the frequency of abnormal mitotic cells in ALL
patients may be prognostically less significant than that in
1982
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2925
Y. Kaneko et al.
ANLL patients.
Our study indicates that the karyotype contributes additional
prognostic information about response to therapy independent
of age and WBC. In some A1 or A2 patients, the karyotype
was more reliable in predicting a poor prognosis than were
other factors. A chromosome study is now essential for predic
tion of the prognosis for ALL patients.
ACKNOWLEDGMENTS
The authors thank Margaret Johnson and Dianne Gallagher for data manage
ment; Paulette Martin, M. Gelida Egues. Marie Harén,and Raphael Espinoza for
technical assistance; Elisabeth Lanzl for editorial review; and Karen Gordon for
secretarial assistance.
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CANCER
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Karyotype and Clinical Features in ALL
Fig. 1. Karyotype with Q-banding of a cell from Patient 13 at diagnosis. .Arrows, abnormal chromosomes forming a reciprocal translocation. Karyotype is
46,XX,t(1;19Xq21;q13).
Inset, partial karyotype of a cell from the same patient at relapse; arrows, abnormal chromosomes. del(3Xq23) and del(11Xq21), in addition
to t(1;19), indicating karyotypic progression.
Fig. 2. Partial karyotype with Q-banding of a cell from Patient 15. Arrows, abnormal chromosomes
JULY
forming t(11;14Xq13;p13).
1982
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2927
V. Kaneko et al.
Fig. 3. Top, partial karyotype with Q-banding of a cell from Patient 22; Arrows, abnormal chromosomes forming t(16;17Xp13;q23). Bottom, same chromosomes
as those at top with regular Giemsa staining.
limns »i
tod i
c
f
o
n
iA
M
io
v»
17 .
18
«* ti
Fig. 4. Karyotype with Q-banding of a cell from Patient 27. Arrows, abnormal chromosomes forming a 3-way translocation t(5q —
;8q + ;14q+) and a reciprocal
translocation, t(12p+;22q-}.
One of chromosomes 18 had an extra segment of unidentified origin at the terminal portion of the long arm. Karyotype is
46,XX,-18,t(5;8;14Xq11;q24;q32),t(12;22Xp13;q11),
+ der(18)t(18;?Xq23;?). inset, partial karyotype with R-banding of the same metaphase cell.
2928
CANCER
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Karyotype and Clinical Features in ALL
«Kl«
H
lit >l M «»»i
••
if
III
•• «4ft
••
Fig. 5. Karyotype with Q-banding of a cell from Patient 44. Arrows, extra chromosomes 4, 6, 10, 15. 17, 18, 21, 21, and X. mar. marker chromosome. Karyotype
is 56,XXY,+4,+6, + 10, + 15,+ 17,-H8, + 21, + 21. + m
JULY
1982
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2929
Correlation of Karyotype with Clinical Features in Acute
Lymphoblastic Leukemia
Yasuhiko Kaneko, Janet D. Rowley, Daina Variakojis, et al.
Cancer Res 1982;42:2918-2929.
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