[CANCER RESEARCH 52, 1481-1493, March 15, 1992]
Chromosome Abnormalities in Adult T-Cell Leukemia/Lymphoma:
A Karyotype Review Committee Report1
Nanao Ramada, Masaharu Sakurai, Kanji Miyamoto, Isao Sanada, Naoki Sadamori, Shirou Fukuhara, Syuiti Abe,
Yukimasa Shiraishi, Tatsuo Abe, Yasuhiko Kaneko, and Masanori Shimoyama2
Department of Hematology, Research Institute for Nuclear Medicine and Biology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima 734 fN. K.J;
Departments of Cancer Chemotherapy [M. Sa.] and Laboratory Medicine [Y. KJ, Saitama Cancer Center Hospital, SIS Komuro, Ina, Saitama 362; Chromosome
Research Unit, Faculty of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido 060 fS. A.]; Department of Hygiene, Kyoto Prefectural University
of Medicine, Kawaramachidori Hirokoji-agaru, Kamikyo-ku, Kyoto, Kyoto 602 [T. A.]; Department of Hematology, Atomic Disease Institute, Nagasaki University
School of Medicine, 7-1 Sakamoto machi. Nagasaki, Nagasaki 852 [N. S.]; First Division of Internal Medicine, Faculty of Medicine, Kyoto University, S3 ShogoinKawaramachi, Sakyo-ku, Kyoto, Kyoto 606 ¡S.F.J; School of Health Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama, Okayama 700 [K. M.J; Second
Department of Internal Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, Kumamoto 860 [I. S.]; Department of Anatomy, Kochi Medical
College, Kohasu, Okatoyo-cho, Nangoku, Kochi 781-51 [Y. S.]; and Hematology-Oncology and Medical Oncology Division, National Cancer Center Hospital, 5-1-1
Tsukiji, Chuo-ku, Tokyo 104 [M. Sh.J, Japan
ABSTRACT
Karyotypes of 107 cases with adult 'I'-cell leukemia/lymphoma (58
male, 49 female; 81 acute or lymphoma type, 26 chronic or smoldering
type) were reviewed by a panel of cytogeneticists and were correlated
with the subtypes of the disease. Clonal chromosome abnormalities were
found in 103 (96%) cases, of which four had hypotetraploidy. Of 184
numerical abnormalities in the remaining 99 cases with near- or pseudodiploidy, trisomies for chromosomes 3 (21% of cases), 7 (10%), and
21 (9%), mnnosonty for X chromosome (38%) in the female, and loss of
a Y chromosome (17%) in the male were more frequent than expected
(/' < 0.01). Of 373 structural abnormalities in all the 103 aneuploid
cases, trenslocations involving 14q32 (28%) or 14qll (14%) and deletion
of 6q (23%) were most frequent, followed by deletion of lOp (9%), 3q
(8%), Sq, 9q, and 13q (7% each), and Ip and 7p (6% each). The proportion
of cases with aneuploid clones (with > or < 46 chromosomes), the
average numbers per case of both numerical and structural abnormalities,
and marker chromosomes were larger in the aggressive acute or lym
phoma type than in the nonaggressive chronic or smoldering type (/' <
0.01). The combination of rearrangement in 14q32 and monosomy X
(seven cases) or deletion of lOp (six cases), and that of trisomy 3 and
deletion in 6q21 (six cases), occurred only in the acute or lymphoma type
and may be associated with the aggressiveness in adult T-cell leukemia/
lymphoma.
INTRODUCTION
ATL3 is a clinical entity defined by specific clinicohematological features including the association with HTLV-I virus and
pleomorphic leukemic "flower cells" with deeply indented or
lobulated nuclei and a T-cell-specific surface marker profile (14). The occurrence of ATL shows an uneven geopathological
distribution with a much higher incidence in southwestern
Japan than in any other part of the world.
Chromosome findings in ATL have been reported from sev
eral laboratories in Japan. Although trisomies for chromosomes
3 (5, 6) and 7 (6, 7), deletions of the long arm of chromosome
6 (5), and structural rearrangements involving band 14qll (8)
or 14q32 (5) have been described as major chromosome
changes, no specific abnormalities have been found in ATL (9,
Received 2/21/91; accepted 1/6/92.
The costs of publication of this article were defrayed in part by the payment
of page charges. This article must therefore be hereby marked advertisement in
accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1Supported by Grants-in-Aid for Cancer Research (59S-1, 62S-1, and 2S-1)
from the Ministry of Health and Welfare of Japan.
2To whom requests for reprints should be addressed.
3 The abbreviations used are: ATL, adult T-cell leukemia/lymphoma; HTLVI, human T-cell leukemia/lymphoma virus type I; IWCL, International Workshop
on Chromosomes in Leukemia/Lymphoma; A+L, "acute" and "lymphoma" types
of ATL; C+S, "chronic" and "smoldering" types of ATL; RSCA, related single
cell abnormalities; USCA, unrelated single cell abnormalities; TCRA, T-cell
receptor a chain gene; TCRB, T-cell receptor ß
chain gene; TCRD, T-cell receptor
ti chain gene.
10). Attempts to correlate chromosome abnormalities with the
clinical subtypes of the disease (6, 8) have provided only incon
clusive results.
In order to determine the incidence of various chromosome
abnormalities seen in Japanese ATL, we established an ad hoc
committee, collected ATL cases from all over Japan, and con
ducted a joint review of karyotypes. This paper describes the
consensus karyotypes and their correlation to the clinical sub
types in 107 cases with ATL. We were unable to find any
abnormality specific to ATL, but were able to clarify that most
abnormalities, be they numerical or structural, tend to appear
more frequently in the aggressive acute or lymphoma type than
in the nonaggressive chronic or smoldering type.
MATERIALS AND METHODS
The Committee. The "ATL Karyotype Review Committee 1985
(ATLKRC85)" (M. Shimoyama, chairperson) was organized ad hoc in
1985 to review both clinical and cytogenetic data.on then published
and unpublished cases with ATL in Japan. The committee consisted of
the 11 authors of this paper and was sponsored by the study group,
"Multidisciplinary Treatment of Solid Cancer," which was being sup
ported by grants from the Ministry of Health and Welfare of Japan.
Queries. Clinical data including WBC and the percentage of abnor
mal lymphocytes in the peripheral blood, positivity for anti-HTLV-I
antibody, the patient's survival time, and the subtype diagnosis of ATL,
i.e. acute type (1), lymphoma type (4, 11), chronic type (11), or smol
dering type (4, 11), or pre-ATL (12), were submitted for each case
before the joint review in 1985. The method of tumor cell culture was
also ascertained. Additional clinical and laboratory data were collected
for most (105 of 107) cases in 1989 to confirm the originally diagnosed
subtype of ATL. The survival data were updated simultaneously.
The Patients. A total of 139 cases with ATL were submitted from 16
institutions. Twelve cases were submitted with karyotypes prepared by
commercial laboratories. For all the other cases, chromosomes were
analyzed in either the current authors' laboratories or other hospitals
under the supervision of the authors.
The clinical diagnoses given by original hospitals were reviewed
centrally by members of the committee on the basis of the submitted
clinical data. Pathology slides of lymph nodes from 31 cases were
reviewed by members of the Lymphoma Pathology Panel of Japan, and
their consensus diagnoses helped in the classification of some borderline
cases.
Review of Karyotypes. Twelve cytogeneticists (including all the au
thors except for M. Shimoyama, who served as a moderator, and two
others) reviewed the karyotypes. The committee met 7 times at the
National Cancer Center in Tokyo, Japan, during 1985 and 1986 and
spent 13 full days for reviewing. At least 3 karyotypes from each clone
were reviewed by 5 to 10 (most often 7) cytogeneticists. The Interna
tional System for Human Cytogenetic Nomenclature (ISCN) (13) was
used for description of karyotypes. An abnormal clone was defined as
2 or more cells with the same structural rearrangement or extra chro-
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CHROMOSOMES IN ADULT T-CELL LEUKEMIA/LYMPHOMA
mosome, or 3 or more cells with the same missing chromosome. One
single normal metaphase was considered as sufficient evidence of a
normal clone. Debatable karyotypes were finalized at plenary meetings.
Methods Used in Chromosome Studies for the Accepted Cases. Chro
mosome analyses had been performed on peripheral blood in 81, lymph
node in 18, bone marrow in 6, and pleural effusion or ascites in 2 cases.
The samples were cultured for varying lengths of time (within 6 h in
18, 24 h in 51, 48 h in 6, 72 h in 18, and 120 h or over in 14 cases).
Either phytohemagglutinin, T-cell growth factor, or recombinant interleukin 2 was used for culture in 13 cases. Chromosomes were analyzed
by G- and/or Q-banding.
Data Analysis. All collected data were analyzed by ACOS System
750, using a previously reported program for karyotype (14), and a
commercially available BMDP program for clinical data. Significance
for the difference was evaluated by the t test between the average
numbers, by the x2 or Fisher's exact test between the proportions, and
by the generalized Wilcoxon and Mantel-Cox tests between the survival
RESULTS
Clinical Findings. Of the 139 cases submitted, 32 were re
jected because of central diagnosis of a disease other than ATL,
previous therapy, inadequate karyotypes, or other reasons. Of
the 107 cases accepted as adequately studied, 31 were from
Okayama, 17 were from Kumamoto, 13 were from Nagasaki,
10 were from Kyoto (Kyoto University), 9 were from Sapporo,
and 8 were from Kochi; the remaining 19 were from various
other centers (Table 1). Thirty-one of the 107 cases had been
accepted for the Fifth IWCL (34) (Table 1). Individual karyotypic data were not published as part of the workshop report.
Central review of the original clinical diagnoses indicated
difficulty in the differentiation between the acute and lymphoma
types or between the chronic and smoldering types for some
cases. Accordingly, the acute type and the lymphoma type, and
the chronic type and the smoldering type (or pre-ATL), were
combined, respectively, and 81 were classified as having the
A+L type, and 26 were classified as having the C+S type (Tables
1 and 2). Survival times are not different between the acute and
lymphoma or between the chronic and smoldering type of
patients (35).
There was a slight male predominance in the accepted cases
(not significant). Thirteen cases were under 40 yr of age, 17
cases were in the 40s, 30 cases were in the 50s, 30 cases were
in the 60s, and 17 cases were 70 yr or over; the ages ranged
from 24 to 77 yr with a median of 58 yr. There was no significant
difference in the age distribution between the A+L and C+S
groups (Table 2).
Immunologie-ai studies were performed for 90 cases. In all
these cases, the tumor cells formed E-rosettes or reacted with
one or more monoclonal antibodies against T-cell-associated
antigens. The anti-HTLV-I antibody was tested in 93 patients;
it was positive in 91, with titers ranging from 1:20 to 1:1280,
and negative in 2. The 2 HTLV-I-negative cases were out of 3
cases submitted from an institution located in an ATL-nonendemic area where HTLV-I-negative ATL was being extensively
studied. They were examined for proviral DNA of HTLV-I and
exhibited no signs of viral integration (28); these patients had
49% and 96% of "flower cells" typical of ATL in the peripheral
blood, respectively.
Abnormal clinical and laboratory findings, except for the
bone marrow involvement and skin lesions, were significantly
more frequent in the A+L type than in the C+S type of patients
(Table 2). Hypercalcemia, hyperbilirubinemia, and hepatosplenomegaly were never or only occasionally seen in the C+S type
of patients, but were frequent in the A+L type of patients. The
C+S type of patients survived longer than did the A+L type of
patients (P< 0.01).
Karyotypes. The karyotypes of the 107 accepted cases are
given in Table 1. Of these, 34 cases have been reported with
the revised karyotypes after the joint review (8, 15, 16, 18, 24,
27, 28, 30, 31, 33); 28 cases were only reported before it with
the original karyotypes (5, 6, 17, 19, 20-23, 25, 26, 29, 32),
and 45 cases have never been reported.
Four cases (Patients 9, 73, 81, and 103) had no clonal
abnormalities. A total of 103 cases (96%) had clonal chromo
some abnormalities; 89 cases had only one abnormal clone, and
14 had 2 or more abnormal clones, 4 (Patients 5, 83, 106, and
107) of which had clones unrelated to each other (Table 3).
USCA were seen in 17 patients. Sixty-one patients (59%), i.e.,
41 (52.5%) in the A+L group and 20 (80%) in the C+S group,
had cells with a normal karyotype besides those with an abnor
mal one. Four (Patients 59, 64, 80, and 87) had complex
hypotetraploid karyotypes, and numerical changes were not
described for these karyotypes since the precise number of lost
or gained chromosomes was not always determinable. Of the
remaining 99 cases with near- or pseudodiploidy, 3 had only
numerical abnormalities, 9 had only structural abnormalities,
and 87 had both types of abnormalities.
Modal Chromosome Numbers. Modal chromosome numbers
by clinical subtype are shown in Table 3. Aneuploidy (hypo- or
hyperdiploidy or hypotetraploidy) was more frequent in the
A+L type than in the C+S type (P < 0.01).
Numerical Chromosome Abnormalities. There were 184 of
gain or loss of whole chromosomes in 90 of the 99 near- or
pseudodiploid cases (Table 4). Numerical abnormalities, pre
ponderantly loss of chromosomes, occurred more frequently in
the A+L type than in the C+S type (P < 0.01).
Trisomy for chromosome 3 (21 cases, 21%), 7 (10 cases,
10%), or 21 (9 cases, 9%) and monosomy for X chromosome
in the female (17 cases, 38%) or loss of a Y chromosome in the
male (9 cases, 17%) occurred more frequently than expected (P
< 0.01) (Fig. 1; Table 5). All these abnormalities, except trisomy
21, occurred more frequently in the A+L type than in the C+S
type, but only with borderline significance (0.05 < P < 0.1)
(Table 5). There was no age dependency in the incidence of X
chromosome loss occurring in lymphoma cells in the ages over
40; loss of an X chromosome was seen in 4 of 7, 3 of 9, 8 of
19, and 2 of 7 females in the 40s, 50s, 60s, and 70s, respectively.
Only 3 female patients were under 40 yr and did not show loss
of an X chromosome.
Marker chromosomes also occurred more frequently in the
A+L type than in the C+S type (P < 0.01) (Table 4).
Structural Chromosome Abnormalities. A total of 373 struc
tural chromosome abnormalities were observed in 100 of the
103 cases with abnormal karyotypes, including the 4 hypotetra
ploid cases (Table 4). Translocations (derivative chromosomes)
with an unidentified chromosome segment were most frequent,
followed by partial deletions, balanced (reciprocal) transloca
tions, and unbalanced translocations (derivative chromosomes
with an identified chromosome segment).
Breaks relating to rearrangements (including translocations,
inversions, etc.) occurred most frequently in band 14q32 (31
breaks in 29 cases), followed by band 14qll (14 cases) (Fig. 2;
Tables 5 and 6). The only recurrent rearrangement was inver
sion of 14q, which involved both 14ql 1 and 14q32 and occurred
in 6 cases. The most common abnormality involving band
14q32 was translocation of an unknown chromosome segment
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CHROMOSOMES IN ADULT T-CELL LEUKEMIA/LYMPHOMA
Table 1 Consensus karyotypes of 107 patients with ATL attained by the ATLKRC8S
Patient
Center0
Age,
sex
Source
No. of
cells
analyzed
Ref.*
Karyotype
Acute (A) and lymphoma (L) types
46, XX (60%)/47, X, -X, -4, -7, -12, -16, +20, inv
dup (1) (q21 -»q32), del (2) (q33), inv (9) (p24q22),
del ( 13) (q 12q3 1), t (3; 14) (q 12; q32), -t-der (4) t (4; ?)
(pli; ?), +der (7) t (7; 12) (q32; ql3), +3mar (40%)
820
58F
BM'
10
860
49M
PB
14
47, XY, -1, -3, -5, +7, -10, -14, del (10) (pl2), +der
(1) t (1; ?) (q42; ?), +der (3) t (3; ?) (ql2; ?), +der (5) t
(5; ?) (q35; ?), +der (10) t (10; ?) (q24; ?), +der (14) t
17(3)
3'
870
41M
PB
18
46, XY (6%)/47, XY, -2, +8, t (6; 17) (q21; pl3), -l-der
(2) t (2; 3) (q37; pi 1) (77%)/RSCA (1 1%)/USCA (6%)
5(9)
4
940
51M
PB
15
50, X, -Y, -13, -15, -17, -20, +21, inv (I)(pl3q23),
+i ( 1) (qter -»q23::p 13 -»cen -»p 13::q23 -»qter),
+der ( 1q3p), +der ( 15) t (7; 15) (q2 1; q24), +der ( 17) t
(Y; 17) (ql 1; pl2), +der (20) t (20; ?) (pl3; ?), +3mar
(67%)/50, X, -Y, -15, -17, -20, +21, inv (1), +i (1),
+der ( 1q3p), +der ( 15), +der ( 17), +der (20), +2mar
(33%)
800
61M
LN
22
46, XY (5%)/48, XY, -1, +der (1) t (I; ?) (pll; ?), +der
(4) t (4; ?) (q27; ?), +mar (50%)/92, XXYY, 2p-,
llp+, 12q+(45%)
/«(N55)
870
63F
PB
17
46, XX (6%)/47, XX, +3, -16, -21, dup (1) (q21 -»
q32), t (6; 13) (p23; ql4), +der (16) t (16; ?) (pl3; ?),
+der (21) t (21; ?) (pll; ?) (88%)/RSCA (6%)
5(10)
830
83M
PB
810
51M
LN
52
46, XY (31%)/47, XY, +3, -17, del (1) (p36), del (6)
(q21), +der (17) t (17; ?) (pl3; ?) (54%)/RSCA (15%)
75(10), 16 (7)
46, XY (57%)/53, X, +X, -Y, - 1, -6, +7, +8, - 17,
-19, del (1) (q25), +del (3) (ql2), +dup (3) (p23p25),
+der (1) t (1; ?) (q23; ?), +der (6) t (6; ?) (q21; ?), +der
(19) t (19; ?) (p 13; ?), +der (?) t (1; ?) (q25; ?), +der
(?), +der (?), +mar (43%)
9
810
59M
PB
30
46, XY (97%)/USCA (3%)
10
820
73F
BM
12
46, XX (8%)/48, XX, +7, -8, -8, -10, +12, -19, -21,
del (3) (q21q25), del (6) (ql5q21), +del (6), del (9)
(p22), +der (8) t (8; ?) (q?; ?), +der ( 19) t ( 19; ?) (q 13;
?), +2mar (92%)
75(1), 16 (\)
11
820
68M
PB
12
49, XY, +3, -6, -17, -18, -18, +der (6) t (6; ?) (ql5;
?), +der (18) t (18; ?) (pi 1; ?), +der (18) t (18; ?) (q23;
?), +3mar (100%)
15(1), 16(6)
12
820
54F
PB
20
46, XX (70%)/47, XX, -4, -5, +7, -8, -11, -17, -18,
t (7; 11) (q22; p 15), +der (8) t (8; ?) (q?; ?), +der ( 17) t
(17; ?) (p?; ?), +der (18) t (18; ?) (pll; ?), +3mar
(30%)
15(3), 16 (\0)
13
820
24M
PB
14
820
44F
PB
48, XY, -2, +3, -9, del (6) (q21q25), dup (7) (qll -.
q22), +der (7q9p), +der (2) t (2; ?) (q3?; ?), +mar
(100%)
47, XX, -3, +7, -14, -14, del (9) (:pl2-. q32:), t (7;
12) (ql 1; pl3), +der (3) t (3; ?) (ql3; ?), +der (14) t
(14; ?) (pi 1; ?), +der (14) t (14; ?) (q32; ?) (100%)
15 (8), 76(12)
15
82016
+der46,
XX, -1, +3, del (6) (q21q25), del (10) (p 13),
(\\)15(6),16
82017
XY (33%)/47, XY, +3, -14, t (5; 7; 6) (qlS; q22;
(67%)47,
q21), +der (14) t (14; ?) (q24; ?)
12
16 (\3)
XX, -16, t (10; 14) (pll; qll), +der (16) t (16; ?)
(q23;?), +mar(100%)15(4),
" 800, Saitama Cancer Center (Saitama); 810, Hokkaido University (Sapporo); 820, Kyoto University (Kyoto); 830, Kyoto Prefectural University of Medicine
(Kyoto); 840, Hiroshima University (Hiroshima); 850, Nagasaki University (Nagasaki); 860, Kochi Medical College (Nangoku, Kochi); 870, Okayama Blood Center
(Okayama); 880, Kumamoto University (Kumamoto); 890, National Cancer Center (Tokyo); 900, Ryukyu University (Okinawa); 910, Fukuoka University (Fukuoka);
920, Aichi Cancer Center (Nagoya); 940, Jikei University Aoto Hospital (Tokyo); 970, Kokura Memorial Hospital (Kitakyushu, Fukuoka).
* The italicized references were published after the joint review by ATLKRC85. The numbers or letters in parentheses refer to cases in each reference. Twentyeight cases were reported only before the review, 20 were reported only after the review, and 14 were reported both before and after the review; 45 cases have been
reported neither before nor after the review.
' BM, bone marrow; PB, peripheral blood; LN, lymph node; PE, pleural effusion; AS, ascites.
•¿*
Case accepted for the Fifth IWCL.
' der (14) t (14; ?) (q32; ?) and one of the markers may possibly be products of t (14; 14) (qll; q32).
^Anti-HTLV-I antibody-negative cases. No proviral DNA of HTLV-I was detected in either of these cases. The antibody was not tested for Cases 5, 21, 28, 29,
30, 31, 32, 34, 59, 66, 70, 85, and 86. All the other cases were anti-HTLV-I antibody positive.
83065F46M33FPBPBPB1012447,
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CHROMOSOMES
IN ADULT T-CELL LEUKEMIA/LYMPHOMA
Table 1 Continued
No. of
cells
analyzed
Patient
Center0
Age,
sex
18
840
49M
PB
31
19
840
39M
PB
18
48, X, -Y, -3, -3, -9, - 12, - 13, - 14, del (9) (q 13q22),
+der (1) t (?; 1) (1; ?) (?; pllq42; ?), +der (3) t (3; ?)
(pl3; ?), +der (9) t (3; 9) (pl3; pl3), +der (12) t (12; ?)
(q24; ?), +der (13) t (13; ?) (ql4; ?), +der (14) t (14; ?)
(q32; ?), +3mar (83%)/USCA (17%)
20"
850
48F
PB
15
47, X, -X, +3, -4, +15, inv (14) (qllq32),
?) (q35; ?) (93%)/RSCA (7%)
21'
850
55M
PB
25
45, X, -Y, -2,
del ( l ) (q42),
t (2; ?) (p25;
(11; ?) (q25;
(100%)
22'
850
56M
PB
27
48, XY, +15, -22, +del (14) (qllq32),
q32), +mar(100%)
23'
850
57F
PB
21
46, X, -X, -10, -12, -14, -17, +der (14) t (14; ?) (q32;
?), +4mar (62%)'/RSCA (38%)
«(7),19(23), 20(10)
24'
850
68F
PB
24
44, X, -X, -1, -3, -5, -10, -12, -13, -14, -17, -17,
-18, del (14) (qllql3), +der (1) t (1; ?) (p36; ?), +der
(3) t (3; ?) (q29; ?), +der (14) t (14; ?) (q32; ?), +der
(17) t (17; ?) (q25; ?), +5mar (100%)'
«(5), 19 (13), 20 (11)
25'
850
62F
PB
21
48, X, -X, +2, -4, - 14, del (5) (q 13), del ( 14) (q 11q 13),
+der (4) t (4; ?) (pl6; ?), +der (14) t (14; ?) (q32; ?),
+2mar (52%)'/RSCA (48%)
«(2), 19(10), 20(2)
26'
850
52M
PB
20
46, XY (5%)/47, XY, -2, +3, -6, +7, -14, -15, +der
(1 1) t (1 1; 14) (pl3; ql3), +der (2) t (2; ?) (q37; ?), +der
(6) t (6; ?) (p25; ?) (95%)
«(1), 19(9), 20(5)
27'
850
68M
PB
20
46, XY, -4, -9, -10, -12, del (1) (p32), +der (4) t (4; ?)
(pl6; ?), +3mar (95%)/RSCA (5%)
«(4), 19 (12), 20 (7)
28
860
47F
PB
15
46, XX (7%)/46, X, -X, +3, -13, -14, -14, -17, -18,
-19, del (2) (pl5p22), del (6) (q21), del (6) (ql3q25),
del (18) (pi 1), +der (13) t (13; ?) (q34; ?), +der (14) t
(14; ?) (q24; ?), +der (14) t (14; ?) (q32; ?), +der (17) t
3;?), +2mar (93%)
17(2)
29
860
62F
PB
16
46, XX (13%)/47, XX, -2, +3, -5, -13, -14, del (10)
(p 12), del (10), +der (2) t (2; ?) (q37; ?), +der (5) t (5;
?) (q31; ?), +der (13) t (13; ?) (q34; ?), +der (14) t (14;
?) (q32; ?) (81%)/RSCA (6%)
17(8)
30
860
40F
PB
16
46, XX (13%)/48, X, -X, -3, -4, -7, +11, -14, -21,
+der (3) t (3; ?) (q25; ?), +der (7) t (4; 7) (ql2; q36),
+der (21) t (21; ?) (q22; ?), + 4mar (87%)
31'
870
36M
PB
10
46, XY (10%)/46, XY, del (9) (ql2q32), inv (14) (ql Iq32),
t (1; 7) (p36; q21), t (12; 15) (ql3; q26) (90%)
5 (21), 22 (1), 23 (2),
24(2)
32'
870
29M
PB
10
46, XY (10%)/48, Y, -X, +3, +del (1) (pi2), t (5; 14)
(q22; q32), +mar (60%)/RSCA (30%)
S (17), 23 (1), 25 (2)
33"
870
45M
PB
11
46, XY (55%)/47, XY, +3, del (8) (pl2), t (1; 22) (q23;
pl3), t (5; 19) (ql3; pl3), t (6; 17) (p21; q23) (45%)
5(25)
34'
870
58F
PB
10
45, XX, -3, -10, -13, -17, -19, -20, inv (2) (p23q33),
del (15) (q23), i (18q), +der (20) t (17; 20) (ql 1; pl3),
+der (3) t (?; 3) (3; ?) (?; p25q21; ?), +der (10) t (10; ?)
(pli; ?), +der (13) t (13; ?) (ql4; ?), +der (19) t (19; ?)
(pl3; ?) (50%)/RSCA (50%)
5 (22), 23 (7)
35'
870
44M
PB
11
46, XY (27%)/46, XY, -7, -9, -19, del (3) (q27), i (14q),
+der (9) t (9; 19) (pi 1; pi 1), +der (7) t (7; ?) (q36; ?),
+der (19) t (?; 9) (9; 19) (?::9p24 -»9pll::19pll
-»
19qter) (37%)/45, X, -Y, -7, -9, -19, del (3), i (14q),
+der (9), +der (7), +der (19) (27%)/RSCA (9%)
24(1)
36"
870
72F
PB
10
46, XX (10%)/46, X, -X, +4, del (5) (ql3q22), t (6; 7)
(ql5; q32), t (8; 10) (q24; q22) (70%)/RSCA (20%)
5 (11), 24 (2)
37'
870
54M
PB
13
46, XY (15%)/46, X, -Y, +3, -4, -9, -19, del (1) (p34),
del (10) (pi2), del (13) (ql3), del (14) (q21), +der (4) t
(4; ?) (q34; ?), +der (9) t (9; ?) (p22; ?), +der (19) (pi3;
?) (46%)/46, X, -Y, +3, -4, -7, -9, -19, del (1), del
(10), del (14), del (15) (q21), +der (4), +der (7) t (7; ?)
(q22; ?), +der (9), +der (19) (39%)
5 (24), 23 (12), 26(1)
Source
Ref.*
Karyotype
47, XY, -l, -4, -12, +18, del (7) (p 14), del (13) (q32),
+der (4) t (4; 12) (q31; ql3), +der (1) t (1; ?) (q42; ?),
+mar (100%)
+der (4) t (4;
-3, -3, -5, -8, -9, -11, -15, -16, -17,
+del (6) (q2 1), inv ( 14) (q 11q32), +der (2)
?), +der (3) t (3; ?) (p21; ?), +der (11) t
?), +der (15) t (15; ?) (pli; ?), +5mar
t (14; 14) (qll;
«(6),19(21), 20(6)
«(8), 19 (24), 20 (9), 21
«(3), 19 (11), 20 (3)
1484
Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1992 American Association for Cancer Research.
CHROMOSOMES IN ADULT T-CELL LEUKEMIA/LYMPHOMA
Table 1 Continued
Age,
sex
No. of
cells
analyzed
Ref.*
Patient
Center"
38
870
60F
PE
39'
870
78F
870
51M
4 1'
870
77M
PB
42'
870
46M
PB
10
46, XY (10%)/47, XY, -15, +21, dup (2) (q21 -»q31),
del (5) (qllql3), del (6) (ql5q21), del (7) (pl5), del (9)
(ql2q22), t (10; 14) (q21; q32), +der (15) t (15; ?) (q26;
?) (90%)
43
870
58M
PB
13
52, X, -Y, +5, +7, +1 1, -14, -16, +21, del (3) (q27),
+del (3) (q21q25), +del (3) (q21q25), del (6) (ql5q21),
+del (9) (q22), del (13) (ql4q32), +der (16) t (7; 16)
(qll; q24), +der (14) t (14; ?) (p 12; ?) (46%)/RSCA
(54%)
870
72F
PB
12
46, XY (8%)/47, XX, t (4; 9) (pl2; p22), +mar (92%)
45
870
76F
PB
4
47, X, -X, +3, -6, -6, +der (X) t (X; ?) (qll; ?), +der
(6) t (6; ?) (ql2; ?), +der (6) t (6; ?) (ql4; ?) (100%)
46
870
64M
PB
10
46, XY (50%)/47, XY, -1, +7, dup (1) (q21 -»q42), del
(9) (ql2q22), t (10; 20) (pi 1; pi 1), +der (1) t (1; ?) (p35;
?) (50%)
47
870
56M
PB
15
47, XY, -13, -18, +21, del (5) (ql3ql5), t (3; 14) (p25;
ql 1), +der (13) t (3; 13) (pl3; pi 1), +der (18) t (18; ?)
(q23; ?) (53%)/46, XY, t (3; 14) (47%)
24(5), 27
48
880
58F
LN
10
47, XX, -10, +del (3) (ql2q27), del (6) (ql3q23), t (3; 7)
(ql3; q32), +der (10) t (10; ?) (q26; ?) (70%)/RSCA
(30%)
6(5)
49
880
70M
PB
25
46, XY (28%)/47, XY, -10, -14, +18, +der(10) t (1; 10)
(qll; pl3), +der (14) t (14; ?) (q32; ?) (72%)
50
880
74M
PB
11
48, XY, -2, -6, -7, -20, +21, +dup(3)(pter-»p21::p25
-> p21::p25 -> qter), +der (2) t (2; ?) (q31; ?), +3mar
(73%)/RSCA (27%)
6(7)
51
880
71F
PB
39
46, XX (64%)/45, X, -X (13%)/USCA (23%)
6(9)
52
880
62F
PB
5
47, XX, +3, -10, -14, +der(10) t (10; ?)(q26; ?) del (10)
(pi 1), +der (14) t (14; ?) (q32; ?) (80%)/RSCA (20%)
53
880
29M
PB
10
48, XY, -2, +5, -13, -14, +der (1) t (1; ?) (pl3; ?), +der
(2) t (2; ?) (q33; ?), +der (13) t (13; ?) (q22; ?), +mar
(90%)/RSCA(10%)
54
880
45F
PB
10
46, XX (20%)/47, XX, -2, -3, +7, -9, -14, del (2)
(q33q37), del (15) (q24), t (4; 12) (pl6; qll), +der (3) t
(3; ?) (pi 3; ?), +der (9) t (9; ?) (q34; ?), +2mar (80%)
55
880
59M
PB
890
71M
PB
134
46, XY (49%)/43, X, -1, -2, -4, -6, -8, -9, -9, -10,
-13, -14, -15, -16, -18, -20, +21, -22, del (6) (p21),
t (Y; 4) (qll; q31), +der (1) t (1; 14) (pl3; qll), +der
(2) t (?; 2) (2; ?) (?; pl6q31; ?), +der (9) t (9; ?) (p22; ?),
+der(13)t (13; ?) (pll; ?), +der (14) t (14; ?)(pll;?),
+der (15) t (15; ?) (pi 1; ?), +der (18) t (18; ?) (pi 1; ?),
+4mar (34%)/4n, same abnormalities (17%)
2«(1)
Si'
890
43F
PB
10
48, X, -X, -5, -12, +der (5) t (5; 12) (q22; ql3), +der
(3) t (3; ?) (ql2; ?), +3mar (100%)
28 (2)
58
890
34M
PB
12
45, XY, -7, - 13, - 16, - 17, del (4) (p 14), t (9; 20) (p 13;
pll), +der(16)t(13;
16) (qll; qll), +der (17) t (7; 17)
(q22; P13), +der (7) t (7; ?) (q22; ?) (92%)/RSCA (8%)
59
900
61M
PB
18
46, XY (83%)/83, XX, -Y, -Y, del (1) (p34), del (6)
(ql3q21), inv (14) (ql Iq32), del (16) (ql3), der (1) t (1;
?) (p36; ?), der (5) t (5; ?) (pl3; ?), der (5) t (5: ?) (q33:
?), der (6) t (6; ?) (ql3; ?), etc. (17%)
40'
10
Karyotype
46, XX (10%)/47, X, -X, +3, del (6) (ql5q21), del (13)
), +mar (60%)/RSCA (30%)
5(6), 23(11)
PB
20
46, XX (5%)/47, XX, + 3 (95%)
5 (26), 26 (4)
PB
24
46, XY (4%)/48, XY, -1, -14, +21, del (6) (ql5), +der
(1) t (1; ?) (p36; ?), +der (3) t (3; ?) (p21; ?), +der (?) t
(14; ?) (ql 1; ?) (80%)/RSCA (8%)/USCA (8%)
5 (14), 24 (3), 26 (6)
Source
47, XY, -6, -9, - 18, del (9) (q22), +der (6) t (6; ?) (q 15;
?), +der (9) t (9; ?) (p22; ?), -t-der (18) t (18; ?) (q21; ?),
+der(I8)(100%)
5 (3), 23 (5)
47, XY, -1, +3, -4, -13, -15, -18, -22, +del (X) (q24),
del (6)(p21), +der(15)t (1; 15)(pll; pll), +der (1) t
(1; ?) (pi 1; ?), +der (18) t (18; ?) (pi 1; ?), +der (22) t
(22; ?) (ql 1; ?), +mar (60%)/RSCA (40%)
1485
Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1992 American Association for Cancer Research.
Table 1 Continued
No. of
cells
analyzed
Patient
Center"
Age,
sex
Source
60
900
60M
BM
20
61
910
66F
PB
15
46, XX (60%)/48, XX, -7, -17, -18, -19, +der(7) t (7;
?) (q32; ?), +der (11) t (11; ?) (pli; ?), +der (19) t (19;
), +3mar(40%)
62
810
57M
BM
30
46, XY (43%)/45, XY, +2, -4, -4, -7, -14, -19, -21,
+ 4mar (20%)/RSCA (7%)/USCA (30%)
63
810
37M
LN
32
46, XY (6%)/50, XY, +7, -14, +del (6) (ql3q25), +der
(14) t (14; ?) (q32; ?), +2mar (56%)/51, XY, +7, +12,
-14, +del (6), +der (14), +2mar (16%)/RSCA (22%)
64
810
53F
LN
23
90, XXXX, der(l) t (1; ?)(pll;
etc. (26%)/RSCA (74%)
65
810
65F
LN
26
66
820
52M
AS
15
49, XX, +4, +8, +18, t (2; 3) (q35; p23) (69%)/RSCA
(31%)
44, -X, die (Y) (ql2), -2, -3, -4, -8, -10, +13, -14,
-16, -17, -19, -19, del (5) (q31q33), i (7q), del (8)
(p21), t (14; 18) (qll; pll), +psudic (4) t (4; 8) (pl6;
p21), +der (X) t (X; ?) (p22; ?), +der (2) t (2; ?) (p23;
?), +der (3) t (3; ?) (pl3; ?), +der Qg) t (10; ?) (pl5; ?)
del (10) (q24), +der (14) t (14; ?) (pl2; ?), +der (16) t
67
820
66F
LN
21
46, XX (10%)/46, X, -X, -4, -11, -13, -14, -14, -16,
del (7) (p 15), i ( 18q), +der (4) t (4; ?) (q3 1; ?), +der (11)
t (1 1; ?) (q23; ?), +der (14) t (14; ?) (pl2; ?), +der (?) t
(14; ?) (qll; ?), +3mar (90%)
68'
850
49F
LN
27
47, XX, -2, -5, -6, +11, -12, -14, -16, -18, del (5)
(ql 1), del (6) (qlS), del (10) (q24), +der (2) t (2; ?) (p25;
?), +der (5) t (5; ?) (q31; ?), +der (6) t (6; ?) (p23; ?),
+4mar (96%)/RSCA (4%)
69'
850
74M
LN
22
46, XY (5%)/47, XY, +3 (90%)/RSCA (5%)
LN
20
45, X, -Y (80%)/RSCA (20%)
19(2)
46, XX (18%)/46, XX, -14, +der (14) t (14; ?) (q32; ?)
(46%)/47, XX, -14, +del (1) (p 13), +der (14) (18%)/
RSCA(18%)
31(2)
70'
850
35M
Ref.*
Karyotype
46, XY (15%)/46, X, -Y, -14, -15, del (5) (q31), del (7)
(pl3), +der (14) t (14; ?) (q32; ?), +der (15) t (15; ?)
(pli; ?), +mar (80%)/USCA (5%)
?),der(l),
der(l), 16mar,
29(3)
29(7)
19(1), 30 (B)
71
880
28F
PB
11
72
880
53M
PB
11
45, X, -Y, -1, -6, -10, -13, -14, -17, -22, inv (14)
(qllq32), +der (1) t (1; ?) (q32; ?), +der (14) t (14; ?)
(q32; ?), +der (22) t (22; ?) (ql3; ?), +4mar (73%)/
RSCA (18%)/USCA (9%)
31 (S)
73
880
53M
LN
12
46, XY (42%)/USCA (58%)
31(3)
74
880
62F
LN
10
46, X, -X, -13, -14, del (6) (q21q23), +3mar (90%)/
RSCA (10%)
31(6)
75
880
51M
LN
11
46, XY (18%)/46, XY, t (2; 2) (p25; q21) (82%)
il (10)
76
880
59F
LN
13
46, X, -X, -9, -14, +der (9) t (9; ?) (ql3; ?), +der (14) t
(14; ?) (pi 1; ?), +mar (62%)/47, X, -X, -8, -9, -14,
+21, +der (9), +der (14), +2mar (31%)/RSCA (7%)
31(9)
77
910
62F
LN
49
46, XX (14%)/47, X, -X, -1, -3, -11, -14, -15, -16,
-18, -22, +der (1 1) t (1; 11) (pl2; ql4), +der (15) t (1;
15) (q21; pll), +der (1) t (1; ?) (pl2; ?), +der (3) t (3;
?) (q21; ?), +der (3) t (3; ?) (P25; ?), +der (14) t (14; ?)
(pll; ?), +der (16) t (1 1; 16) (ql4; ql3), +3mar (78%)/
USCA (8%)
78
920
66M
PB
12
46, XY, -9, -14, -16, -18, del (6) (q22), del (7) (pll),
del (10) (pi 3), +der (9) t (9; ?) (q34; ?), +der (14) t (14;
?) (q32; ?), +der (16) t (16; ?) (ql3; ?), +der (18) t (18;
?) (pll;?) (100%)
79
970
67M
LN
27
46,XY(19%)/45, Y,-X,-1,
-3, -5, -9, -10, -15, -16,
- 17, - 18, -20, del (3) (q 12q2 1), del (6) (q 15), +del ( 13)
(q32), inv (14) (ql Iq32), +der (X) t (X; ?) (q26; ?), +der
(3) t (3; ?) (pl3; ?), +der (5) t (5; ?) (pl3; ?), +der (9) t
(9; ?) (pl3; ?), +der (10) t (1; ?; 10) (Ipter -»
Ipl3::?::10pll
-» lOqter), +der (?) t (1; ?) (q23; ?),
+3mar(81%)
15(14), 16 (9), 29 (U)
80
970
46F
LN
10
46, XX (20%)/89, XXX, -X, del (7) (pi 3), del (10) (pll),
der (14) t (7; 14) (pi 3; pl3), der (2) t (2; ?) (p23; ?), der
(8) t (8; ?) (p23; ?), mar etc. (
15(15), 16(5), 29(6)
81
860
42F
BM
20
46, XX (100%)
1486
Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1992 American Association for Cancer Research.
CHROMOSOMES
PatientCenter"Age,
sexSourceNo.
IN ADULT T-CELL LEUKEMIA/LYMPHOMA
Table 1 Continued
of
cells
analyzedKaryotypeRéf.'Chronic
types828384'8586"878889"90"91"9293"94"9596979899100101102103104"10510610781083085085086086086087087087081087087087087087088088090097087081087087088087070M3
(C) and smoldering (S)
(36%)48,
XY, -19, +mar (64%)/RCA
+der(14)
Y, -X, +5, -7, -14, -14, +del (6) (ql4q21),
+der(7)
t (1; 14) (pi 1; q21), +der (3) t (3; ?) (q21; ?),
(60%)/46,
t (7; ?) (pi 1; ?), +der (14) t (14; ?) (pi 1; ?)
(6;48, Y, -X, -6, +der (3) t (3: ?) (ql2; ?), +der (6) t
(3)(q2l),
XX, +X, +4, -10, -12, -14, +18, -19, -21, del
?)(q22; del (11) (q23), del (17) (q23), +der (10) t (10;
?)(q32;?), +der (12) t (12; ?) (q24; ?), +der (14) t (14;
(4%)47, ?), +der (21) t (21; ?) (pi 1; ?) (96%)/RSCA
(20%)46,
XX, +3 (80%)/RSCA
1)(73%)46,
XY (27%)/46, XY, del (8) (q24), t (9; 21) (p22; ql
?)(p23;
XY (12%)/89, XXYY, del (6) (q21), der (6) t (6;
(pli;?) ?), der (13) t (13; ?) (pl3; ?), der (?) t (1; ?)
(6%)46,
etc. (82%)/RSCA
(60%)/RSCA(12%)46,
XX (28%)/46, XX, inv (15) (pl3q22)
(90%)46,
XY (10%)/46, XY, inv ins (6) (p23q21ql3)
(6)5
(7), 23 (14), 32
(ql5q21).t
XY (10%)/47, XY, -7, del (1) (q32), del (6)
t(18;
(4; 5) (q33; ql3), +der (7) t (7; ?) (q22; ?), +der (18)
-»ql2::ql2
?) (q21; ?) (40%)/47, X, -7, inv dup (Y) (pter
t(4;
-> ql 1:), del (1), del (6), del (13) (q22q32),
(20%)46,
5), +der (7), +der (18) (30%)/RSCA
(4)5(15)5
(4), 23 (6), 32
(10;46,
XX (92%)/46, XX, -10, del (6) (q21), +der (10) t
+3mar(12%)/USCA(35%)46,
XY (53%)/49, XY, -6, del (3) (ql3), +del (3),
(92%)46,
XY (8%)/50, XY, +3, +6, +2mar
(5)5(13)6(10)ÃŽ5(16),
(17), 23 (13), 32
+der(10)
XX (44%)/47, XX, +X, -10, del (6) (ql5q21),
+der(10)
t (10; ?) (q26; ?) (25%)/46, XX, -10, del (6),
(6%)46,(I9%)/RSCA (6%)/USCA
t(3;
XX (5%)/48, XX, -3, +22, del (10) (pl4), +der (3)
(5%)46,
?) (ql2; ?), +mar (90%)/USCA
(q22;?)
XY (13%)/46, XY, -12, -13, +der (12) t (12; ?)
(87%)46,
del (12) (pl2), +der (13) t (13; ?) (q34; ?)
+der(7)
XY (10%)/46, XY, -7, -14, del (6) (ql5q25),
(90%)46,
t (7; ?) (q35; ?), +der (14) t (14; ?) (q32; ?)
(42%)46,
XX (42%)/46, X, del (X) (q26) (16%)/USCA
(2%)/USCA(11%)46,
XY (81%)/47, XY, +mar (6%)/RSCA
del(10)
XY (45%)/47, XY, -4, -9, -9, -19, -21, -22,
?)(q21;
(p 13), +der (3) t (3; ?) (q29; ?), +der (4) t (4;
(45%)/USCA(10%)46,
?), +der (19) t (19; ?) (pl3; ?), +4mar
(93%)46.
XY (7%)/47, XY, +21, del (6) (ql5q21)
/6(15)24(4)5(19)33
(7;14)
XX (13%)/46, XX, -7, -14, +20, -22, +der (7) t
(87%)46,
(pi 1; ql 1), +der (14) t (14; ?) (q32; ?)
(100%)46,
XX
(92%)46,
XX (8%)/46, XX, dup (7) (q22 -»q32)
+der(10)t(10;?)(q24;?)(90%)46,
XX (10%)/46, XX, -10, t (3; 14) (q21; q32),
(2%)/47,XX,
XX (82%)/45, X, -X, (3%)/47, XX, +X
(12%)46,
+mar (1%)/USCA
-X(17%)/46,
XX, -19, t (1; 14) (p36; q32), +mar (55%)/45, X,
t(2;
XX, -2, -14, del (10) (q22q24), +der (2)
(17%)/RSCA(11%)19(14)17(5)5
?) (q37; ?), +der (14) t (14; ?) (q32; ?)
1487
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CHROMOSOMES IN ADULT T-CELL LEUKEMIA/LYMPHOMA
Table 4 Frequencies of numerical and structural chromosome abnormalities in
patients with ATL by clinical subtype
Table 2 Clinical and laboratory findings in 107 patients
with ATL by clinical subtype
ATLMale/femaleAge
Subtype of
ATLNumerical
26)13/1360.5
=
abnormalities'Gain
chromosomes'Loss
of
chromosomes'Total
of
lossesMarker
of gains and
chromosomes'Structural
(yr)MedianRangeWBC(xlOVliter)MedianRange%
(26)28-7612.4(26)4.6-130.020
abnormalities'Translocations''
*Translocations
anunidentifiedwith
segment'Partial
(81)3.1-287.041
of leukemic cells in pe
bloodMedianRangeBone
ripheral
(72)0-9680'
involvementLymphadenopathy
marrow
Subtype of
7559
=
(0.79)f103
(0.46)22
1
(1.37)162(2.16)98(1.31)n
(0.92)14
(0.58)n
258
=
10369184*IOSIS373PNS*<0.01<0.01
7861
=
(0.78)158*
(0.32)26(1.04)19
(2.03)86(1.10)15320(4.10)C+Sn
deletionsOther
abnormalities'TotalA+Ln
(23)1-9081C(21)55
9970114184112n=
=
2411(0.46)1
=
(0.76)053(2.12)Totaln
(69)85
" Four cases with hypotetraploid karyotypes (3 in A+L and 1 in C+S) were
(22)14(21)10(21)23
(74)60
(%)Hepatomegaly
not included.
(%)Splenomegaly
(72)36
* Each type of abnormality was counted only once when there were 2 or more
(72)42(71)87
(%)Skin
of the same abnormality.
(22)38(21)0(21)0(12)366
(%)High
lesions
' Numbers in parentheses, average number per case.
dehy-drogenase
serum láclate
(70)45
d NS, not significant.
(%)Hypercalcemia
'Apparently identical marker chromosomes in a karyotype were counted
(69)33
(%)Hyperbilirubinemia
repeatedly, since whether or not they were truly identical was often unknown.
(54)160
(%)Survival
f Different abnormalities on a chromosome were counted separately.
(days)1*MedianRangeA+L45/3657(81)'24-8320.1
'Includes 31 balanced and 24 unbalanced translocations, 10 inversions, one
(25)4-4,
(75)5-2,
pseudodicentric,
one dicentric, one insertion, and one isochromosome which
748+C+S(n
426PNS°NS<0.01<0.05NS<0.01<0.01<0.05NS<0.01<0.01<0.05<0.01
apparently occurred in a chromosome with an inversion.
* Also includes 4 translocations in Cases 10, 12 (2 translocations), and 13, for
" NS, not significant.
* Numbers in parentheses, number of cases for which relevant information was
which the breakpoint was not exactly determinable.
' Includes 4 isochromosomes, 2 derivative chromosomes each consisting of 2
available.
' Percentage of cases with a positive finding.
whole arms from different chromosomes, and 9 chromosomes with a partial
* From the day of the chromosome test. + after the number of days indicates
duplication.
that the patient with the longest survival is still living.
Table 3 Number of abnormal clones and modal chromosome number of the
primary clone ¡npatients with A TL by clinical subtype
ATLNo.
clones012
of abnormal
25-
Subtype of
813699(1)"n
=
261205(3)"n
=
10748914
20
moreModal
or
theprimary
chromosome no. of
clone*<444546
(4)°n=
15
103392637244
250112(48.0)'651Totaln=
=
783814(17.9)'31193C+Sn
=
ID
(abnormal)4748-5383-90
(hypotetraploid)A+Ln
* Numbers in parentheses, cases with unrelated clones (Cases 5, 83, 106, and
107).
* Cases with 46 chromosomes (pseudodiploidy) were less frequent, and cases
with other numbers of chromosomes (aneuploidy) were more frequent (P< 0.01)
in the A+L group than in the C+S group.
' Numbers in parentheses, percentage.
to this band, and it was seen in 19 cases. Other recurrently
affected bands included Ipil (7 cases), 3pl3, 7q22 and 18pll
(6 cases each), Ipl3, Ip36, Iq23, 3ql2, 9p22, and 14pll (5
cases each), and 2q37, 4pl6, 6p23, 6q21, 7q32, lOpl 1, 12ql3,
and 17pl3 (4 cases each).
Deletion occurred most frequently on 6q (24 cases, 23%),
followed by 10p (9 cases, 9%), 3q (8 cases, 8%), 5q, 9q, 13q,
Ip, and 7p (Fig. 3; Table 5). The deleted segment on 6q involved
all or a part of 6q21 in 23 of 24 cases. Other overlapping deleted
segments included Ip36—»Ipter
(6 cases), 7pl5—>7pter(6
cases), and 10pl4—»lOpter
(9 cases) (Fig. 3).
Structural abnormalities as a whole, preponderantly deriva
tive chromosomes with an unknown segment (P < 0.01), and
balanced and unbalanced translocations (P < 0.05) occurred
more frequently in the A+L type than in the C+S type (Table
"LOT.
1234567
Chromosome
$
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X Y
10
Io
'S
15-
20
Fig. 1. Distribution of 70 gains and 114 losses of whole chromosomes in 99
cases of ATL with abnormal karyotypes. Four hypotetraploid cases were not
included. Trisomies 3, 7, and 21 were more frequently observed than expected (/'
< 0.01). Monosomy X in the female and loss of a Y in the male were also seen
in increased frequencies (P< 0.01, respectively). Monosomy X in the female, loss
of a Y in the male, and trisomy of 3 or 7 were more frequent in the A+L type
than in the C+S type, but with only borderline significance (0.05 < P < 0.10).
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CHROMOSOMES IN ADULT T-CELL LEUKEM1A/LYMPHOMA
Table 5 Major numerical and structural chromosome abnormalities in patients
with A TL by clinical subtype
and 71) had a clone with a single structural abnormality
[t(3;14)(p25;ql 1) and -14, +der(14)t(14;?)(q32;?), respectively]
ATLNumerical
Subtype of
and another clone with abnormalities additional to the primary
change. One patient (Patient 99) had an unknown marker
242012/121/120/12n
=
992110917/452/549/54n=
=
751910815/331/429/42n
=
abnormalities+3+7+21-XFemaleMale-Y,
chromosome as a single abnormality. One case (Patient 106)
had 3 clones with different single abnormalities, i.e., one with
loss of an X, one with additional X, and the other with a marker
chromosome.
Additional Abnormalities. Two or more related clones were
maleStructural
detected in 10 patients (Patients 4, 35, 37, 47, 56, 63, 71, 76,
90, and 94). Six trisomies, 6 monosomies, 7 deletions, 10
=781325*667176776C+Sn
=2514*02070021Totaln
10314296g7246797P°0.0620.0530.0760.0840.0950.094
abnormalitiest(14qll)t(14q32)del(lp)del(3q)del(5q)del(6q)del(7p)del(9q)del(lOp)del(13q)A+Ln
derivative chromosomes, one reciprocal translocation, one in
version duplication, and 4 markers were seen as additional
abnormalities. No particular autosomes or chromosome bands
were specifically involved in additional abnormalities, either
numerically or structurally. There was an excess of the involve
ment of sex chromosomes (2 monosomies X, 2 trisomies X,
one missing Y, and an inversion duplication of a Y) as expected.
"Obtained
by Fisher's exact test. Values greater than 0.100 are not given.
Trisomy 3, trisomy 7, loss of an X in the female, loss of a Y in the male,
translocation with a break in 14qll, and translocation with a break in 14q32
occurred more frequently in the A+S type than in the C+S type, but only with
borderline significance (0.05 < P < 0.10).
* One each in both groups had two 14q32 translocations (cf. Table 6).
4). Individually, however, translocations with a break in band
14qll or band 14q32 were the only structural abnormalities
that occurred more frequently in the former than in the latter,
although the incidences differed only with borderline signifi
cance (Table 5).
More than one of the aforementioned structural and numer
ical abnormalities occurred together in many cases. Besides the
cases with inv(14q), 4 had rearrangements in both 14qll and
14q32. Rearrangement in 14q32 was associated with monosomy X in 7 cases. Trisomy 3 and deletion in 6q21, and
rearrangement in 14q32 and deletion in 10p, occurred together
in 6 cases each. All these combinations occurred only in the
A+L type.
Translocations and Inversions Possibly Involving the TCR or
IGH Genes. Fourteen cases (14%) had translocations involving
band 14qll containing TCRA and TCRD gene loci (Fig. 2;
Table 6). In addition, the 14ql 1 break occurred in 3 deletions
(Fig. 3). Three cases may possibly have had a break in band
7q35 where the TCRB gene has been assigned (Table 6).
Band 14q32 (sites of the IGH gene, AKT1, and a putative
protooncogene TCL1) was involved in translocation (or inver
sion) with a known chromosome band in 12 cases and with an
unknown chromosome segment in 19 (Table 6). A 14q32 break
also occurred in an interstitial deletion (Fig. 3).
There were 39 balanced translocations, including 4 inver
sions, or unbalanced translocations, not listed in Table 6. None
of these abnormalities was the same, although there were bands
in which breaks occurred in association with more than one
abnormality, as can be seen in Fig. 2.
Cases with a Single Chromosome Abnormality. Fourteen ATL
cases had only a single abnormality. Three cases (Patients 39,
69, and 85) had a single trisomy 3, which was the only single
abnormality that was seen in more than one patient. One case
each had loss of an X (Patient 51) or a Y (Patient 70) chro
mosome as a single abnormality.
inv(15)(pl3q22) (Patient 88), inv ins(6)(p23q21ql3) (Patient
89), dup(7)(q22-»q32) (Patient 104), del(X)(q26) (Patient 98),
and t(2;2)(p25;q21) (Patient 75) were seen as a single structural
abnormality in one patient each. Two other cases (Patients 47
DISCUSSION
We reported here the clinical and cytogenetic findings ob
tained from 107 adequately studied ATL patients. These cases
included almost all cases of ATL whose chromosomes had been
studied by 1985 in Japan. The karyotypes and the clinical
diagnoses were reviewed by a committee formed by the current
authors. Ninety-eight % of the patients tested for anti-HTLVI antibody showed a positive result. The clinical features of the
HTLV-I-negative cases were the same as those of the antibodypositive patients (28, 36, 37).
Four cases showed only cells with a normal karyotype.
Whether these were ATL cells or nonmalignant cells is uncer
tain. The fact that 3 cases had chromosomally unrelated clones
may indicate that ATL could arise with a normal karyotype,
and that chromosome abnormalities could appear later. DetecTable 6 Inversions and translocations possibly involving T-cell receptor or
immunoglobulin genes in 103 patients with ATL
Abnormality
No. of
cases
Abnormalities probably affecting TCRA or TCRD
genes in Band 14qll
inv(14)(qllq32)
der(l)t(l;14)(pl3;qll)
t(3;14)(p25;qll)
der(7)t(7;14)(pll;qll)
t(14;14)(qll;q32)
Abnormalities possibly affecting TCRB genes in
Band 7q35
der(7)t(4;7)(qI2;q36)
der(7)t(7;?)(q35;?)
der(7)t(7;?)(q36;?)
Abnormalities possibly affecting IGH genes or a
putative oncogene in Band 14q32
6*»
inv(14)(qllq32)
\'
t(l;14)(p36;q32)
t(3;14)(ql2;q32)
t(3;14)(q21;q32)
t(5;14)(q22;q32)
t(10;14)(q21;q32)
a
t(14;14)(qll;q32)
19"
der(14)t(14;?)(q32;?)
" Counted also for 14ql 1 abnormalities.
*One case (Patient 72) also had der(14)t(14;?)(q32;?).
' This case (Patient 107) also had der(14)t(I4;?)(q32;?).
'One case (Patient 72) also had inv(14)(ql Iq32), and one other case (Patient
107) also had I(l;14)(p36;q32).
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CHROMOSOMES IN ADULT T-CELL LEUKEMIA/LYMPHOMA
IS
18
D
3
Q
17
18
18
Fig. 2. Distribution of chromosome breaks in 103 cases of ATL with abnormal karyotypes. The breaks in 4 hypotetraploid cases were also counted. A total of 139
breaks due to 31 balanced and 24 unbalanced translocations, 10 inversions, and 4 other abnormalities (a pseudodicentric, a dicentric, an insertion, and a complex
isochromosome) are depicted on the left, and 180 breaks due to translocations with unknown chromosome segments are depicted on the right of each chromosome.
The exact breakpoints for derivative chromosomes of this type were not determinable (Table 4, Footnote h) and hence are not depicted here. Breaks occurred most
frequently in band 14q32 (29 cases), followed by band 14ql 1(14 cases). Other recurrently affected bands included lpt1 (1 times); 3pl3, 3ql2, 7q22, and 18pl 1 (6
times); Ipl3, Ip36, Iq23, 3ql2, 9p22, and 14pl 1 (5 times each); 2q37, 4pl6,6p23, 6q21, 7q32, lOpl 1, 12ql3, and 17pl3 (4 times each), etc. There were no recurrent
translocations or inversions except for inv(14)(ql Iq32), which was observed in 6 cases.
Recurrent chromosomal breaks in T-cell neoplasia including
tion of only normal or simple abnormal karyotypes at diagnosis
and later appearances of complex karyotypes at relapse have ATL have been reported to occur in bands 6ql5-q21 (5-8, 44been described in serially studied ATL patients (6, 28, 38). The 48), 14qll (5, 8, 45, 46, 49, 50), and 14q32 (5-8, 17, 45, 46).
Also in this study structural abnormalities involving these bands
higher incidence of aneuploidy in the aggressive A+L patients
than in the nonaggressive C+S patients is a reflection of the were most frequently observed (Figs. 2 and 3). inv(14)(ql Iq32)
difference in the complexity of karyotypes between these 2 was the only recurrent rearrangement in the present series of
groups. Previous studies on T-cell lymphomas or chronic T- ATL cases.
Partial deletions of chromosomes were most frequent in 6q,
cell leukemias have reported lower incidences of aneuploid
clones than the present study (18, 39-42).
where all or a part of band 6q21 was commonly (in 23 of 24)
The present study demonstrated high frequencies of recurrent
deleted (Fig. 3). Deletion of 6q has been reported in lymphoid
malignancies including acute lymphoblastic leukemia and nonnumerical chromosome changes such as trisomies for chromo
somes 3, 7, and 21 and monosomy for X in the female or loss Hodgkin's lymphoma (18, 34, 39, 51). Particularly, it has been
of a Y in the male (Table 5; Fig. 1). Previous observations have found in a large proportion of Japanese cases of ATL (5, 34)
or American cases of HTLV-I-positive leukemia-lymphoma
only emphasized trisomy 3 (5, 6, 43) or 7 (6, 7, 43) as a major
numerical change in ATL. We do not really know whether or (47), all or a part of band 6q21 being deleted in almost all the
not the loss of an X chromosome occurred depending on age; cases that had a 6q deletion. Since in no cases were consecutive
chromosome studies done, we were not able to confirm the
only 3 patients were less than 40 yr of age, and the incidence
of the loss in younger patients was not known. Although the previous findings that 6q abnormalities were associated with
the aggressive course, short survival and clinical parameters
incidence of numerical abnormalities as a whole, especially that
of chromosome loss, was significantly higher in the A+L type indicating these features, and also occurred in later stages (47,
52). No difference existed in the incidence of 6q abnormalities
than in the C+S type, no individual chromosomes were proven
between the A+L type and the C+S type in the present series.
to be involved more frequently in one group than in the other
A gene (or genes) suppressing lymphomagenesis of ATL may
with any meaningful significance.
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CHROMOSOMES IN ADULT T-CELL LEUKEMIA/LYMPHOMA
5
6
i 8
17
IB
19
M
21
K
X
Y
Fig. 3. Distribution of 180 partial chromosomal deletions in 103 ATL patients with abnormal karyotypes. Deletion occurred most frequently on 6q, almost always
(in 23 of 24) involving all or a part of 6q21. Overlapping deletion was also seen in segments Ip36—»Ipter
(6 cases), 7pl5—>7pter(6 cases), 10pl4-»10pter (9 cases),
reside in 6q21. Protooncogene MYB is located in 6q22-23 (51). 6q21. All these combinations occurred in cases in the A+L
Band 6q22 was deleted in 18 of the 24 cases in our study, which group and may have been associated with the aggressiveness of
contrasted to an observation (48) that this band was consistently the disease.
Some of the bands in which breaks recurrently occurred
bordered by the chromosomal breakpoints, and that MYB se
quences, which the investigators located precisely in 6q22, were contain loci for known or putative protooncogenes; MYB,
unaffected. Other recurrently deleted regions, such as Ip36- MET, and AKT1 and TCL1 genes have been located to 6q22pter, 7pl5-pter, or 10pl4-pter, may also contain genes with q23, 7q31-q32, and 14q32, respectively (48, 51, 54, 55). Also,
similar tumor-suppressing effects. All or a part of 13ql4, the TCR genes have been shown to be rearranged with known or
band in which the tumor suppresser gene RB (retinoblastoma) putative protooncogenes or unidentified genes in T-cell malig
nancy-associated chromosome translocations involving 14qll
resides, was deleted in 4 of our cases.
Deletion or rearrangement of 7q has been reported in T-cell (TCRA and TCRD) and 7q35 (TCRB) (51, 54, 55). The
leukemias including ATL (7, 45). In this series no deletion of inv(14)(qllq32) and other 14q32 translocations have break
7q was observed (Fig. 3), although translocation and duplication points in either the Kill locus or a region proximal to it, and,
if the break occurred in the latter, may involve a T-cell-related
of 7q were seen in 11 and 2 patients, respectively.
Deletion 5q has been said to be rather common in lymphoid protooncogene (54, 55).
Trisomy 3 was the only single abnormality that appeared in
disorders (53). The deletions were interstitial in 4 and terminal
in 3 cases in our series, and they were not distinguishable from more than one patient. This trisomy was observed as a single
abnormality in 2 cases of T-cell diffuse mixed lymphoma be
those found in myeloid disorders (53).
sides an ATL patient at the fifth IWCL (34) and may merit
As in the case of numerical abnormalities, structural abnor
malities occurred more frequently in the A+L than in the C+S consideration as a primary change in T-cell malignancies.
In conclusion, the present study on a large number of ATL
type as a whole; however, none of the translocations or deletions
was more frequently seen in the former than in the latter with cases, whose karyotypes were reviewed by a panel of cytogeneacceptable significance. Marker chromosomes also occurred ticists, provided evidence that the complexity of chromosome
abnormalities is associated with the clinical subtype of ATL,
more frequently in the former.
More than one of the numerical and structural abnormalities although none of the abnormalities found was proven to be
often occurred in the same case in combination. Most frequent specificto ATL. The increase in the complexity of chromosome
combinations included rearrangement in band 14q32 and mon- abnormalities in the advanced, aggressive type of ATL suggests
osomy X or deletion lOp, and trisomy 3 and deletion in band that many of the abnormalities seen in such a condition may
1491
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CHROMOSOMES IN ADULT T-CELL LEUKEMIA/LYMPHOMA
16. Fujita, K., Izumi, Y., Sawada, H., Yamasaki, Y., Fukuhara, S., and Uchino,
H. Cytogenetic study on the adult T-cell leukemia. Rinsho Ketsueki, 28:
1385-1393,1987.
17. Shiraishi, Y., Taguchi, T., Kubonishi, I., Taguchi, H., and Miyoshi, I.
Chromosome abnormalities, sister chromatid exchanges, and cell cycle analy
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adult T-cell leukemia lymphocytes.
Cancer Genet. Cytogenet., 15:65-77, 1985.
18. Maseki, N., Kaneko, Y., Sakurai, M., Kurihara, M., Sampi, K., Shimamura,
K., and Takayama, S. Chromosome abnormalities in malignant lymphoma
in patients from Saitama. Cancer Res., 47: 6767-6775, 1987.
19. Sadamori, N., and Nishino, K. The chromosomal findings in patients with
adult T-cell leukemia (ATL) and related disorders. Recent Adv. RES Res.,
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Amagasaki, T., Kinoshita, K., and Ichimaru, M. Abnormalities of chromo
ACKNOWLEDGMENTS
some 14 at Band 14qll in Japanese patients with adult T-cell leukemia.
Cancer Genet. Cytogenet., 17: 279-282, 1985.
We thank Dr. K. Araki, Ryukyu University, Dr. K. Fujita, Kokura
21. Sadamori, N., Kusano, M., Nishino, K., Yamada, Y., and Ichimaru, M. A
translocation between chromosomes 8 and 14 in a Japanese patient with
Memorial Hospital, Dr. N. Tomono, Osaka Red Cross Hospital, Dr.
adult T-cell leukemia. Cancer Genet. Cytogenet., 20: 179-180, 1986.
T. Suchi, Aichi Cancer Center, Dr. M. Kikuchi, Fukuoka University,
22. Miyoshi, I., Miyamoto, K., Sumida, M., Nishihara, R., Lai, M., Yoshimoto,
Dr. I. Miyoshi, Kochi Medical College, and Dr. H. Nagoshi, Jikei
S., Sato, J., and Kinuiru. I. Chromosome 14q+ in adult T-cell leukemia.
Cancer Genêt.Cytogenet., 3: 251-259, 1981.
Medical College, for providing samples for chromosome study; mem
23. Miyamoto, K., Sato, J., Kitajima, K., Togawa, A., Suemani, S., Sanada, H.,
bers (Dr. S. Watanabe, Dr. M. Kikuchi, Dr. K. Nanba, Dr. T. Suchi,
and Tanaka, T. Adult T-cell leukemia. Chromosome analysis of 15 cases.
and Dr. A. Mikata) of the Lymphoma Pathology Panel of Japan for
Cancer (Phila.), 52:471-478, 1983.
reviewing the pathology slides; and Dr. H. V'uniamolo for computer
24. Miyamoto, K., Tornita, N., Ishii, A., Miyamoto, N., Nonaka, H., Kondo, T.,
analysis. We also thank Dr. N. Ochi-Takeuchi and Dr. K. Nishida for
Sugihara, T., Yawata, Y., Tada, S., Tsubota, T., Kitajima, K., and Kimura,
I. Specific abnormalities of chromosome 14 in patients with acute type of
their cooperation in the karyotype review, Dr. N. Maseki for helpful
adult T-cell leukemia-lymphoma. Int. J. Cancer, 40:461-468, 1987.
advice, and N. Kobayashi for clerical assistance.
25. Miyamoto, K., Sato, J., Kitajima, K., Hamazaki, K., Adachi, T., Sato, T.,
Noda, N., Hioka, H., Sanada, H., Tanaka, T., and Taguchi, H. A 14q+
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Chromosome Abnormalities in Adult T-Cell
Leukemia/Lymphoma: A Karyotype Review Committee Report
Nanao Kamada, Masaharu Sakurai, Kanji Miyamoto, et al.
Cancer Res 1992;52:1481-1493.
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