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Abnormalities of chromosome 14 at band 14q11 in Japanese patients with adult T-cell leukemia
SHORT COMMUNICATION Abnormalities of Chromosome 14 at Band 1 4 q l l in Japanese Patients with Adult T-Cell Leukemia Naoki Sadamori, Miyuki Kusano, Kenji Nishino, Masuko Tagawa, Ei-ichi Yao, Yasuaki Yamada, Tatsuhiko Amagasaki, Ken-ichiro Kinoshita, and Michito Ichimaru
A d u l t T-cell leukemia (ATL) is a n e w l y defined clinical entity on the basis of the clinical picture, characteristic m o r p h o l o g y of the abnormal lymphocytes, T-cell markers, geopathologic distribution with a m u c h higher frequency in southwest Japan, and HTLV/ATLV viruses. For the past several years, some specific abnormalities of c h r o m o s o m e #14 involving band 14q32 in various B-cell malignancies have been reported, such as t(8;14)(q24;q32) in Burkitt's l y m p h o m a and B-cell acute l y m p h o b l a s t i c leukemia, t(11;14)(q13;q32) in chronic l y m p h o c y t i c leukemia, and t(14;18)(q32;q21) in follicular l y m p h o m a , as reviewed by Yunis [1]. The translocation between chromosome #14 and others in B-cell malignancies u s u a l l y results in an elongation of the long arm of c h r o m o s o m e #14, w h i c h is u s u a l l y described as 1 4 q + . Cimino et al. [2] suggested that the 14q + m a y be a c h r o m o s o m e marker for B-cell malignancies. On the other hand, achievements in the cytogenetic studies of T-cell malignancies have been scarce. Recently U e s h i m a et al. [3] i n d i c a t e d that most reported patients with T-cell malignancies, such as S~zary syndrome, mycosis fungoides, cutaneous T-cell l y m p h o m a , and T-cell chronic l y m p h o c y t i c leukemia had a rearrangement of the long arm of c h r o m o s o m e #14 with a break at band 14q11-13. Based on this fact, they suggested that the break at 14q11-13 probably constitutes the most c o m m o n n o n r a n d o m a b n o r m a l i t y in T-cell malignancies. Nevertheless, all eight patients with ATL reported by Ueshima et al. [4] and Miyamoto et al. [5] had a c h r o m o s o m e # 1 4 a n o m a l y with a break at band 14q32, like that in B-cell malig-
From the Department of Hematology,Atomic DiseaseInstitute, NagasakiUniversity School of Medicine, Nagasaki, Japan. Address requests for reprints to Dr. Naoki Sadamori, Department of Hematology, Atomic Disease Institute, Nagasaki University School of Medicine, 7-1 Sakamoto-machi, Nagasaki 852 Japan. Received October 5, 1984; accepted November 8, 1984.
279 © 1985 Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017
Cancer Genetics and Cytogenetics 17, 279-282 0165-4608/85/$03.30
Age/sex
61/F 62/F 56/M 56/M 52/M 48/F 68/M 40/M 55/M 57/F 68/F
I(S.S.) 2(F.M.) 3(I.I.) 4(T.S.) 5(K.I.) 6(Y.N.) 7(T.M.) 8(TOO.) 9(M.H.) 10(S.K.) 11(S.H.)
27 21 27 22 20 15 20 24 25 21 24
Total number of metaphases analyzed 21 21 27 19 19 14 19 22 25 13 24
Abnormal metaphases in abnormal clone
A b n o r m a l i t i e s of c h r o m o s o m e # 1 4 i n 11 p a t i e n t s w i t h A T L
Case (initial)
Table 1
48 48 48 48 47 47 46 46 46 45 44
Number of chromosomes
t(12;14)(q24;q11) ÷ t(14;14)(q11-13;q32),del(14)(ql lq1~) + t(14;14)(q11-13;q32),del(14)(qllq13) del(14)(qllq13) ÷ t(11;14)(p11;q11),- 14 inv(14)(qllq32) ÷ t(14;14)(q11-13;q32),del(14)(qllq13) none + der(14)t(14;?)(q11;?),- 14 ÷ t(14;14)(q11-13;q32) ÷ t(14;14)(q11-13;q32),del(14)(qllq13)
Abnormalities associated with chromosome #14
Modal karyotype
281
Abnormalities at Band 1 4 q l l in ATL
~
,,,=p.._
Case 1 12
13 Figure 1
14
14
15
Partial karyotypes of t(12;14)(q24;q11) in case 1, and inv(14)(qllq32) in case 6.
nancies. It appears u n u s u a l that the break on the long arm of c h r o m o s o m e #14 differed between ATL and other T-cell malignancies. The present study is based on observations of 11 typical ATL patients who were examined cytogenetically between January 1980 and December 1983. All these patients were natives of Nagasaki Prefecture, one of the most clustering areas of ATL in Japan. Leukemic cells for cytogenetic study were obtained from the peripheral blood of all patients at the time of diagnosis. Mononuclear cells separated by centrifugation over F i c o l l - H y p a q u e gradients were cultured in RPMI 1640 m e d i u m s u p p l e m e n t e d with 10% fetal calf serum but without any mitogens. The cells were harvested after 1-20 hr. Colcemid was a d d e d 1 or 2 hr before harvesting. In each specimen, at least 15 metaphases were analyzed using G- and Q-banding techniques. The karyotypes of all patients in this series were submitted to the Fifth International W o r k s h o p on Chromosomes in L e u k e m i a - L y m p h o m a , w h i c h was held in Japan on October 1 0 15, 1984. As shown in Table 1, abnormal clones existed in all patients in this series. The m o d a l chromosome numbers ranged from 44 to 48. Six of 11 patients had a reciprocal translocation between chromosome #14 and c h r o m o s o m e #12 (case 1) (Fig. 1) or #14 (cases 2, 3, 7, 10, 11). In one patient (case 5), only the long arm of chromosome #14, w h i c h was translocated to recipient chromosomes, was identified and one patient (case 6) had an inversion of chromosome #14, inv(14)(qllq32), shown in Figure 1. It is interesting to note that the chromosome b a n d i n g pattern revealed the presence of an abnormal chromosome # 1 4 with a break at b a n d 1 4 q l l in all ten patients with ATL associated with abnormal chromosome #14. The data of ATL presented by us s u p p o r t the finding of a break in the u p p e r segment of chromosome #14 in T-cell malignancies, except for the ATL cases r e v i e w e d by Ueshima et al. [3]. We suggest a possibility that the p r o x i m a l 14q rearrangement at band 1 4 q l l in T cells associated with HTLV/ATLV is one of the essential factors for transformation to ATL, and that a reciprocal translocation of t(14;14)(q11-13;q32) is a cytogenetic subgroup of ATL. However, more patients with ATL and other types of T-cell malignancy will have to be studied cytogenetically before a final conclusion can be reached.
282
N. S a d a m o r i et al.
REFERENCES 1. Yunis JJ (1983): The chromosomal basis of human neoplasia. Science 221:227-236. 2. Cimino MC, Roth DG, Colomb HM, Rowley JD (1978): A chromosome marker for B-cell cancers. N Engl J Med 298:1422. 3. Ueshima Y, Rowley JD, Variakojis D, Winter J, Gordon L (1984): Cytogenetic studies on patients with chronic T-cell leukemia/lymphoma. Blood 63:1028-1938. 4. Ueshima Y, Fukuhara S, Hattori T, Uchiyama T, Takatsuki K, Uchino H (1981}: Chromosome studies in adult T-cell leukemia in Japan: Significance of trisomy 7. Blood 58: 420-425. 5. Miyamoto K, Sato J, Kitajima K, Togawa A, Suemaru S, Sanada H, Tanaka T (1983): Adult T-cell leukemia: Chromosome analysis of 15 cases. Cancer 52:471-478.
A d u l t T-cell leukemia (ATL) is a n e w l y defined clinical entity on the basis of the clinical picture, characteristic m o r p h o l o g y of the abnormal lymphocytes, T-cell markers, geopathologic distribution with a m u c h higher frequency in southwest Japan, and HTLV/ATLV viruses. For the past several years, some specific abnormalities of c h r o m o s o m e #14 involving band 14q32 in various B-cell malignancies have been reported, such as t(8;14)(q24;q32) in Burkitt's l y m p h o m a and B-cell acute l y m p h o b l a s t i c leukemia, t(11;14)(q13;q32) in chronic l y m p h o c y t i c leukemia, and t(14;18)(q32;q21) in follicular l y m p h o m a , as reviewed by Yunis [1]. The translocation between chromosome #14 and others in B-cell malignancies u s u a l l y results in an elongation of the long arm of c h r o m o s o m e #14, w h i c h is u s u a l l y described as 1 4 q + . Cimino et al. [2] suggested that the 14q + m a y be a c h r o m o s o m e marker for B-cell malignancies. On the other hand, achievements in the cytogenetic studies of T-cell malignancies have been scarce. Recently U e s h i m a et al. [3] i n d i c a t e d that most reported patients with T-cell malignancies, such as S~zary syndrome, mycosis fungoides, cutaneous T-cell l y m p h o m a , and T-cell chronic l y m p h o c y t i c leukemia had a rearrangement of the long arm of c h r o m o s o m e #14 with a break at band 14q11-13. Based on this fact, they suggested that the break at 14q11-13 probably constitutes the most c o m m o n n o n r a n d o m a b n o r m a l i t y in T-cell malignancies. Nevertheless, all eight patients with ATL reported by Ueshima et al. [4] and Miyamoto et al. [5] had a c h r o m o s o m e # 1 4 a n o m a l y with a break at band 14q32, like that in B-cell malig-
From the Department of Hematology,Atomic DiseaseInstitute, NagasakiUniversity School of Medicine, Nagasaki, Japan. Address requests for reprints to Dr. Naoki Sadamori, Department of Hematology, Atomic Disease Institute, Nagasaki University School of Medicine, 7-1 Sakamoto-machi, Nagasaki 852 Japan. Received October 5, 1984; accepted November 8, 1984.
279 © 1985 Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017
Cancer Genetics and Cytogenetics 17, 279-282 0165-4608/85/$03.30
Age/sex
61/F 62/F 56/M 56/M 52/M 48/F 68/M 40/M 55/M 57/F 68/F
I(S.S.) 2(F.M.) 3(I.I.) 4(T.S.) 5(K.I.) 6(Y.N.) 7(T.M.) 8(TOO.) 9(M.H.) 10(S.K.) 11(S.H.)
27 21 27 22 20 15 20 24 25 21 24
Total number of metaphases analyzed 21 21 27 19 19 14 19 22 25 13 24
Abnormal metaphases in abnormal clone
A b n o r m a l i t i e s of c h r o m o s o m e # 1 4 i n 11 p a t i e n t s w i t h A T L
Case (initial)
Table 1
48 48 48 48 47 47 46 46 46 45 44
Number of chromosomes
t(12;14)(q24;q11) ÷ t(14;14)(q11-13;q32),del(14)(ql lq1~) + t(14;14)(q11-13;q32),del(14)(qllq13) del(14)(qllq13) ÷ t(11;14)(p11;q11),- 14 inv(14)(qllq32) ÷ t(14;14)(q11-13;q32),del(14)(qllq13) none + der(14)t(14;?)(q11;?),- 14 ÷ t(14;14)(q11-13;q32) ÷ t(14;14)(q11-13;q32),del(14)(qllq13)
Abnormalities associated with chromosome #14
Modal karyotype
281
Abnormalities at Band 1 4 q l l in ATL
~
,,,=p.._
Case 1 12
13 Figure 1
14
14
15
Partial karyotypes of t(12;14)(q24;q11) in case 1, and inv(14)(qllq32) in case 6.
nancies. It appears u n u s u a l that the break on the long arm of c h r o m o s o m e #14 differed between ATL and other T-cell malignancies. The present study is based on observations of 11 typical ATL patients who were examined cytogenetically between January 1980 and December 1983. All these patients were natives of Nagasaki Prefecture, one of the most clustering areas of ATL in Japan. Leukemic cells for cytogenetic study were obtained from the peripheral blood of all patients at the time of diagnosis. Mononuclear cells separated by centrifugation over F i c o l l - H y p a q u e gradients were cultured in RPMI 1640 m e d i u m s u p p l e m e n t e d with 10% fetal calf serum but without any mitogens. The cells were harvested after 1-20 hr. Colcemid was a d d e d 1 or 2 hr before harvesting. In each specimen, at least 15 metaphases were analyzed using G- and Q-banding techniques. The karyotypes of all patients in this series were submitted to the Fifth International W o r k s h o p on Chromosomes in L e u k e m i a - L y m p h o m a , w h i c h was held in Japan on October 1 0 15, 1984. As shown in Table 1, abnormal clones existed in all patients in this series. The m o d a l chromosome numbers ranged from 44 to 48. Six of 11 patients had a reciprocal translocation between chromosome #14 and c h r o m o s o m e #12 (case 1) (Fig. 1) or #14 (cases 2, 3, 7, 10, 11). In one patient (case 5), only the long arm of chromosome #14, w h i c h was translocated to recipient chromosomes, was identified and one patient (case 6) had an inversion of chromosome #14, inv(14)(qllq32), shown in Figure 1. It is interesting to note that the chromosome b a n d i n g pattern revealed the presence of an abnormal chromosome # 1 4 with a break at b a n d 1 4 q l l in all ten patients with ATL associated with abnormal chromosome #14. The data of ATL presented by us s u p p o r t the finding of a break in the u p p e r segment of chromosome #14 in T-cell malignancies, except for the ATL cases r e v i e w e d by Ueshima et al. [3]. We suggest a possibility that the p r o x i m a l 14q rearrangement at band 1 4 q l l in T cells associated with HTLV/ATLV is one of the essential factors for transformation to ATL, and that a reciprocal translocation of t(14;14)(q11-13;q32) is a cytogenetic subgroup of ATL. However, more patients with ATL and other types of T-cell malignancy will have to be studied cytogenetically before a final conclusion can be reached.
282
N. S a d a m o r i et al.
REFERENCES 1. Yunis JJ (1983): The chromosomal basis of human neoplasia. Science 221:227-236. 2. Cimino MC, Roth DG, Colomb HM, Rowley JD (1978): A chromosome marker for B-cell cancers. N Engl J Med 298:1422. 3. Ueshima Y, Rowley JD, Variakojis D, Winter J, Gordon L (1984): Cytogenetic studies on patients with chronic T-cell leukemia/lymphoma. Blood 63:1028-1938. 4. Ueshima Y, Fukuhara S, Hattori T, Uchiyama T, Takatsuki K, Uchino H (1981}: Chromosome studies in adult T-cell leukemia in Japan: Significance of trisomy 7. Blood 58: 420-425. 5. Miyamoto K, Sato J, Kitajima K, Togawa A, Suemaru S, Sanada H, Tanaka T (1983): Adult T-cell leukemia: Chromosome analysis of 15 cases. Cancer 52:471-478.