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11q13 is a Cytogenetically Promiscuous Site in Hematologic Malignancies
11q13 is a Cytogenetically Promiscuous Site in Hematologic Malignancies K. F. Wong
ABSTRACT: 11q13 translocation has been described in mantle cell lymphoma in the form of t(11;14) (q13;q32), with rearrangement and over-expression of the cyclin D1 gene. Recently, an association between 11q13 and acute myeloid leukemia is recognized. We describe the occurrence of 11q13 translocations in both acute leukemias and myelodysplastic syndrome, and suggest that other genetic mechanisms unrelated to cyclin D1 may be involved in the tumorigensis. Furthermore, 11q13 appears to be a cytogenetically promiscuous site involved in reciprocal translocations with different chromosomes in both myeloid and lymphoid malignancies. © Elsevier Science Inc., 1999. All rights reserved.
INTRODUCTION Rearrangements of 11q are known to be associated with acute leukemia, with the breakpoints clustered mainly to the 11q23 region [1]. 11q23 translocations are found in diverse types of hematologic malignancies, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), and are associated with different chromosomal aberrations, although they share a common underlying molecular change with the rearranged MLL gene [2]. In this report, we describe six patients with acute leukemia and myelodysplastic syndrome (MDS) showing 11q13 translocation, and provide evidence that 11q13 may be another common site involved in reciprocal translocations with different chromosomes in both myeloid and lymphoid neoplasia similar to that of 11q23. MATERIALS AND METHODS Case Selection Six patients with hematologic malignancies and 11q13 abnormality were identified from the cytogenetic files of the Department of Pathology, Queen Elizabeth Hospital, Hong Kong. They were diagnosed during a 5-year period from 1993 to 1998, and included 3 cases of AML, 1 case of MDS, and 1 case each of T-cell ALL and common ALL.
From the Department of Pathology, Queen Elizabeth Hospital, Hong Kong S.A.R., People’s Republic of China. Address reprint requests to: Dr. K. F. Wong, Department of Pathology, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong S.A.R., People’s Republic of China. Received October 7, 1998; accepted December 17, 1998. Cancer Genet Cytogenet 113:93–95 (1999) Elsevier Science Inc., 1999. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
During the same period, 211 cases of AML and 78 cases of ALL were diagnosed in the Queen Elizabeth Hospital. Cytogenetic Studies Cytogenetic studies were performed by overnight fluorodeoxyuridine synchronized culture of the marrow cells at diagnosis. Metaphase chromosomes were banded by trypsin/ Giemsa and karyotyped according to the ISCN [3]. Immunohistochemical Studies Formalin-fixed paraffin-embedded marrow biopsies were available in four case (cases 2, 3, 5, and 6). The tissue blocks were retrieved and immunohistochemical studies for cyclin D1 expression were performed using the DCS-6 antibody (Dakopatts, Copenhagen, Denmark), with labeled streptokinase-biotin technique on the VENTANA automated immunostainer. A case of mantle cell lymphoma (MCL) with t(11;14)(q13;q32) was used as a positive control. RESULTS Cytogenetic Findings The results of cytogenetic studies are summarized in Table 1. The cytogenetic findings of case 2 has been reported previously [4]. Among the six patients with 11q13 changes, three were in the pediatric age group. 11q13 translocation was the sole abnormality in two patients with AML showing t(7;11)(q36;q13) and t(10;11)(p13;q13) (Fig. 1). A case of refractory anemia with excess of blasts (RAEB) also showed a t(7;11)(q36;q13) as part of a very complex abnormality (Fig. 2A). Several different chromosomes including chromosomes 9, 10, and 17 were involved in the reciprocal translocations with 11q13 in the other three cases (Fig. 2B).
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K. F. Wong Table 1 Cytogenetic findings of hematologic malignancies with 11q13 rearrangement Case
Sex/Age
Diagnosis
Cytogenetic findings
1 2 3
M/6 F/79 F/49
AML-M1 AML-M1 AML-M0
4 5 6
M/64 M/9 F/2
RAEB T-ALL cALL
46,XY,t(10;11)(p13;q13)[17]/46,XY[3] 46,XX,t(7;11)(q36;q13)[16]/46,XX[2] 46,XX,del(2)(q32)[3]/46,XX,der(12;14)(q10;q10),der(17)t(11;17)(q13;p13), 1mar[8]/46,XX[3] 47,XY,del(5)(q33),t(7;11)(q36;q13),18,del(20)(q12),5–100dmin[7] 46,XY,t(10;11)(p11.2;q13),del(11)(q23)[12]/46,XY[15] 54–57,XX,14,16,17,t(9;11)(p13;q13),110,112,114,117,118,120,121, 121,122[cp9]/46,XX[3]
Abbreviations: RAEB, refractory anemia with excess of blasts; T-ALL, T-cell acute lymphoblastic leukemia; cALL, common acute lymphoblastic leukemia.
Immunohistochemical Findings None of the four cases studied was immunoreactive for cyclin D1. For the case of MCL, positive nuclear staining for cyclin D1 could be demonstrated in the lymphoma cells. DISCUSSION Recurrent karyotypic aberrations are sometimes associated with specific subtypes of leukemia. It is, however, unusual for the same chromosomal rearrangement to be found in leukemia of different lineages. Translocated 11q23 with the rearranged MLL gene is a notable exception [5]. Recently, another region in the long arm of chromosome 11, the 11q13, has been found to be frequently rearranged in AML. In fact, it has been suggested that 11q13 translocation is a recurrent karyotypic aberration associated with AML of monocytic lineage [6, 7]. However, this has not been substantiated by our study. On the other hand, we have showed that 11q13 abnormalities could be found in different hematologic malignancies including AML, ALL, and MDS. Among the three patients with AML, one had a t(10;11)(p13;q13) abnormality. This is the fourth case of
AML reported in the literature with such an abnormality [8–10], indicating that t(10;11)(p13;q13) is a recurrent karyotypic aberration in AML. One patient with T-ALL had a t(10;11)(p11.2;q13) abnormality. Translocation (10;11) has been reported as a recurrent karyotypic aberration in T-ALL in the form of t(10;11)(p13z14;q14zq21) [11]. However, the breakpoints in those reported cases were distinctly different from that of ours (Fig. 2). Our results suggest that 11q13 translocation is more commonly found in children with acute leukemia. Among the six patients with 11q13 translocation reported in this study, three of them were pediatric patients, with two having ALL, and one, AML. In fact, a review of the literature shows that 11q13 abnormality is more frequently seen in children and adolescents with AML or ALL [8, 9, 12–18]. Our study further confirms the previous suggestion that apart from 11q23, 11q abnormalities also clustered around the more proximal region of 11q, and in particular, the 11q13 [19]. Similar to the 11q23 region, 11q13 changes can be found in both myeloid and lymphoid neoplasia with different chromosomes serving as donors in the reciprocal translocations [1]. Translocation (11;14)(q13;q32)
Figure 1 (A) GTG-banded karyotype showing 46,XY,t(10;11)(p13;q13) in case 1 and (B) karyogram of the t(10;11)(p13;q13).
11q13 Rearrangement in Leukemia
95 acute lymphobastic and acute myeloid leukemias with 11q23 chromosomal translocations. N Engl J Med 329:909–914. 3. ISCN (1995): An International System for Human Cytogenetic Nomenclature. F Mitelman, ed. S. Karger, Basel. 4. Wong KF, Chu YC. (1998): Acute myeloid leukaemia with a novel t(7;11)(q36;q13) translocation. Cancer Genet Cytogenet 103:71–72. 5. Cleary ML (1993): A promiscuous oncogene in acute leukemia. N Engl J Med 329:958–959. 6. Jani Sait SN, Dal Cin P, Sandberg AA (1987): Recurrent involvement of 11q13 in acute nonlymphocytic leukemia. Cancer Genet Cytogenet 26:351–354. 7. Kwong YL, Lie AK, Chan LC (1993): A novel translocation (3;11)(q26;q13) in a case of acute myelomonocytic leukemia. Cancer Genet Cytogenet 69:158–160. 8. Heim S, Bekassy AN, Garwicz S, Heldrup J, Wiebe T, Kristoffersson U, Mandahl N, Mitelman F (1987): New structural chromosomal rearrangements in congenital leukemia. Leukemia 1:16–23. 9. Pui CH, Williams DL, Raymondi SC, Rivera GK, Look AT, Dodge RK, George SL, Behm FG, Crist WM, Murphy SB (1987): Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia. Blood 70:247–253. 10. Kubonishi I, Seto M, Murata N, Kamioka M, Taguchi H, Miyoshi I (1998): Translocation (10;11)(p13;q13) and MLL gene rearrangement in a case of AML (M5a) with aggressive leukemic cutis. Cancer Genet Cytogenet 104:28–31. 11. Groupe Français de Cytogénétique Hématologique (GFCH) (1991): t(10;11)(p13–14;q14–21): a new recurrent translocation in T-cell acute lymphoblastic leukemias. Genes Chromosom Cancer 3:411–415.
Figure 2 (A) Partial karyotype showing t(7;11)(q36;q13) in case 4 and (B) t(10;11)(p11.2;q13),del(11)(q23) in case 5. G-band with trypsin-Giemsa.
is a characteristic karyotypic aberration in MCL [20]. The PRAD1 (cyclin D1) locus has been identified in the 11q13 region [21], and the translocated 11q13 resulted in rearrangement of the PRAD1 gene, leading to overexpression of its transcript, the cell-cycle protein cyclin D1. However, none of the four cases examined immunohistochemically in this study showed cyclin D1 expression, suggesting that PRAD1 might not be involved in the pathogenesis of the leukemia despite the cytogenetic involvement of 11q13. The involvement of 11q13 in a diversity of chromosomal rearrangements in both myeloid and lymphoid neoplasia is intriguing. It is possible that a variety of breakpoints are involved in 11q13 abnormality which are indistinguishable at the microscopic level. On the other hand, the underlying molecular changes may be similar, despite the fact that different chromosomes are involved in rearrangement with 11q13, as in the case of 11q23 [22]. Further molecular study is required to clarify this. REFERENCES 1. Mitelman F, ed. (1991): Catalog of Chromosome Aberrations in Cancer, 4th Ed. Wiley-Liss, New York. 2. Thirman MJ, Gill HJ, Burnett RC, Mbangkollo D, McCabe NR, Kobayashi H, Ziemin-van der Poel S, Kaneko Y, Morgan R, Sandberg AA, Chaganti RSK, Larson RA, Le Beau MM, Diaz MO, Rowley JD (1993): Rearrangement of the MLL gene in
12. Brodeur GM, Williams DL, Kalwinsky DK, Williams KJ, Dahl GV (1983): Cytogenetic features of acute nonlymphoblastic leukemia in 73 children and adolescents. Cancer Genet Cytogenet 8:93–105. 13. Berger R, Flandrin G, Bernheim A, Le Coniat M, Vecchione D, Pacot A, Derré J, Daniel MT, Valensi F, Sigaux F, OchoaNoguera ME (1987): Cytogenetic studies on 519 consecutive de novo acute nonlymphocytic leukemias. Cancer Genet Cytogenet 29:9–21. 14. Raimondi SC, Kalwinsky DK, Hayashi Y, Behm FG, Mirro J Jr, Williams DL (1989): Cytogenetics of childhood acute nonlymphocytic leukemia. Cancer Genet Cytogenet 40:13–27. 15. Kaneko Y, Rowley JD, Variakojis D, Chilcote RR, Check I, Sakurai M (1982): Correlation of karyotype with clinical features in acute lymphobastic leukemia. Cancer Res 42:2918–2929. 16. Hayashi Y, Ohta Y, Kaneko Y, Sakurai M, Bessho F, Saito F (1985): 11;14 translocation in childhood T-cell acute lymphobastic leukemia. Jpn J Cancer Res 76:160–161. 17. Berger R, Le Coniat M, Derre J, Vecchione D, Chen SJ (1989): Chromosomal rearrangement on chromosome 11q14–q21 in T cell acute lymphobastic leukemia. Leukemia 3:560–562. 18. Huret JL, Heerema NA, Brizard A, Provisor AJ, Benz-Lemoine E, Guilhot F, Savage JRK, Tanzer J (1990): Two additional cases of t dic(9;12) in acute lymphocytic leukemia (ALL): prognosis in ALL with dic(9;12). Leukemia 4:423–425. 19. Heim S, Mitelman F, eds. (1987): Cancer Cytogenetics. Wiley-Liss, New York. pp. 85–87. 20. Raffeld M, Jaffe ES (1991): bcl-l, t(11;14), and mantle cell derived lymphomas. Blood 78:259–263. 21. Motokura T, Bloom T, Kim HG, Jupner H, Ruderman JV, Kronenberg HM, Arnold A (1991): A novel cyclin encoded by a bcl-1 linked candidate oncogenes. Nature 350:512–515. 22. Kwong YL, Tso SC, Wong KF, Tang JKC, Chan TK (1995): Translocational rearrangement of 11q23 in acute monoblastic leukemia. Cancer Genet Cytogenet 82:76–79.
ABSTRACT: 11q13 translocation has been described in mantle cell lymphoma in the form of t(11;14) (q13;q32), with rearrangement and over-expression of the cyclin D1 gene. Recently, an association between 11q13 and acute myeloid leukemia is recognized. We describe the occurrence of 11q13 translocations in both acute leukemias and myelodysplastic syndrome, and suggest that other genetic mechanisms unrelated to cyclin D1 may be involved in the tumorigensis. Furthermore, 11q13 appears to be a cytogenetically promiscuous site involved in reciprocal translocations with different chromosomes in both myeloid and lymphoid malignancies. © Elsevier Science Inc., 1999. All rights reserved.
INTRODUCTION Rearrangements of 11q are known to be associated with acute leukemia, with the breakpoints clustered mainly to the 11q23 region [1]. 11q23 translocations are found in diverse types of hematologic malignancies, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), and are associated with different chromosomal aberrations, although they share a common underlying molecular change with the rearranged MLL gene [2]. In this report, we describe six patients with acute leukemia and myelodysplastic syndrome (MDS) showing 11q13 translocation, and provide evidence that 11q13 may be another common site involved in reciprocal translocations with different chromosomes in both myeloid and lymphoid neoplasia similar to that of 11q23. MATERIALS AND METHODS Case Selection Six patients with hematologic malignancies and 11q13 abnormality were identified from the cytogenetic files of the Department of Pathology, Queen Elizabeth Hospital, Hong Kong. They were diagnosed during a 5-year period from 1993 to 1998, and included 3 cases of AML, 1 case of MDS, and 1 case each of T-cell ALL and common ALL.
From the Department of Pathology, Queen Elizabeth Hospital, Hong Kong S.A.R., People’s Republic of China. Address reprint requests to: Dr. K. F. Wong, Department of Pathology, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong S.A.R., People’s Republic of China. Received October 7, 1998; accepted December 17, 1998. Cancer Genet Cytogenet 113:93–95 (1999) Elsevier Science Inc., 1999. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
During the same period, 211 cases of AML and 78 cases of ALL were diagnosed in the Queen Elizabeth Hospital. Cytogenetic Studies Cytogenetic studies were performed by overnight fluorodeoxyuridine synchronized culture of the marrow cells at diagnosis. Metaphase chromosomes were banded by trypsin/ Giemsa and karyotyped according to the ISCN [3]. Immunohistochemical Studies Formalin-fixed paraffin-embedded marrow biopsies were available in four case (cases 2, 3, 5, and 6). The tissue blocks were retrieved and immunohistochemical studies for cyclin D1 expression were performed using the DCS-6 antibody (Dakopatts, Copenhagen, Denmark), with labeled streptokinase-biotin technique on the VENTANA automated immunostainer. A case of mantle cell lymphoma (MCL) with t(11;14)(q13;q32) was used as a positive control. RESULTS Cytogenetic Findings The results of cytogenetic studies are summarized in Table 1. The cytogenetic findings of case 2 has been reported previously [4]. Among the six patients with 11q13 changes, three were in the pediatric age group. 11q13 translocation was the sole abnormality in two patients with AML showing t(7;11)(q36;q13) and t(10;11)(p13;q13) (Fig. 1). A case of refractory anemia with excess of blasts (RAEB) also showed a t(7;11)(q36;q13) as part of a very complex abnormality (Fig. 2A). Several different chromosomes including chromosomes 9, 10, and 17 were involved in the reciprocal translocations with 11q13 in the other three cases (Fig. 2B).
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K. F. Wong Table 1 Cytogenetic findings of hematologic malignancies with 11q13 rearrangement Case
Sex/Age
Diagnosis
Cytogenetic findings
1 2 3
M/6 F/79 F/49
AML-M1 AML-M1 AML-M0
4 5 6
M/64 M/9 F/2
RAEB T-ALL cALL
46,XY,t(10;11)(p13;q13)[17]/46,XY[3] 46,XX,t(7;11)(q36;q13)[16]/46,XX[2] 46,XX,del(2)(q32)[3]/46,XX,der(12;14)(q10;q10),der(17)t(11;17)(q13;p13), 1mar[8]/46,XX[3] 47,XY,del(5)(q33),t(7;11)(q36;q13),18,del(20)(q12),5–100dmin[7] 46,XY,t(10;11)(p11.2;q13),del(11)(q23)[12]/46,XY[15] 54–57,XX,14,16,17,t(9;11)(p13;q13),110,112,114,117,118,120,121, 121,122[cp9]/46,XX[3]
Abbreviations: RAEB, refractory anemia with excess of blasts; T-ALL, T-cell acute lymphoblastic leukemia; cALL, common acute lymphoblastic leukemia.
Immunohistochemical Findings None of the four cases studied was immunoreactive for cyclin D1. For the case of MCL, positive nuclear staining for cyclin D1 could be demonstrated in the lymphoma cells. DISCUSSION Recurrent karyotypic aberrations are sometimes associated with specific subtypes of leukemia. It is, however, unusual for the same chromosomal rearrangement to be found in leukemia of different lineages. Translocated 11q23 with the rearranged MLL gene is a notable exception [5]. Recently, another region in the long arm of chromosome 11, the 11q13, has been found to be frequently rearranged in AML. In fact, it has been suggested that 11q13 translocation is a recurrent karyotypic aberration associated with AML of monocytic lineage [6, 7]. However, this has not been substantiated by our study. On the other hand, we have showed that 11q13 abnormalities could be found in different hematologic malignancies including AML, ALL, and MDS. Among the three patients with AML, one had a t(10;11)(p13;q13) abnormality. This is the fourth case of
AML reported in the literature with such an abnormality [8–10], indicating that t(10;11)(p13;q13) is a recurrent karyotypic aberration in AML. One patient with T-ALL had a t(10;11)(p11.2;q13) abnormality. Translocation (10;11) has been reported as a recurrent karyotypic aberration in T-ALL in the form of t(10;11)(p13z14;q14zq21) [11]. However, the breakpoints in those reported cases were distinctly different from that of ours (Fig. 2). Our results suggest that 11q13 translocation is more commonly found in children with acute leukemia. Among the six patients with 11q13 translocation reported in this study, three of them were pediatric patients, with two having ALL, and one, AML. In fact, a review of the literature shows that 11q13 abnormality is more frequently seen in children and adolescents with AML or ALL [8, 9, 12–18]. Our study further confirms the previous suggestion that apart from 11q23, 11q abnormalities also clustered around the more proximal region of 11q, and in particular, the 11q13 [19]. Similar to the 11q23 region, 11q13 changes can be found in both myeloid and lymphoid neoplasia with different chromosomes serving as donors in the reciprocal translocations [1]. Translocation (11;14)(q13;q32)
Figure 1 (A) GTG-banded karyotype showing 46,XY,t(10;11)(p13;q13) in case 1 and (B) karyogram of the t(10;11)(p13;q13).
11q13 Rearrangement in Leukemia
95 acute lymphobastic and acute myeloid leukemias with 11q23 chromosomal translocations. N Engl J Med 329:909–914. 3. ISCN (1995): An International System for Human Cytogenetic Nomenclature. F Mitelman, ed. S. Karger, Basel. 4. Wong KF, Chu YC. (1998): Acute myeloid leukaemia with a novel t(7;11)(q36;q13) translocation. Cancer Genet Cytogenet 103:71–72. 5. Cleary ML (1993): A promiscuous oncogene in acute leukemia. N Engl J Med 329:958–959. 6. Jani Sait SN, Dal Cin P, Sandberg AA (1987): Recurrent involvement of 11q13 in acute nonlymphocytic leukemia. Cancer Genet Cytogenet 26:351–354. 7. Kwong YL, Lie AK, Chan LC (1993): A novel translocation (3;11)(q26;q13) in a case of acute myelomonocytic leukemia. Cancer Genet Cytogenet 69:158–160. 8. Heim S, Bekassy AN, Garwicz S, Heldrup J, Wiebe T, Kristoffersson U, Mandahl N, Mitelman F (1987): New structural chromosomal rearrangements in congenital leukemia. Leukemia 1:16–23. 9. Pui CH, Williams DL, Raymondi SC, Rivera GK, Look AT, Dodge RK, George SL, Behm FG, Crist WM, Murphy SB (1987): Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia. Blood 70:247–253. 10. Kubonishi I, Seto M, Murata N, Kamioka M, Taguchi H, Miyoshi I (1998): Translocation (10;11)(p13;q13) and MLL gene rearrangement in a case of AML (M5a) with aggressive leukemic cutis. Cancer Genet Cytogenet 104:28–31. 11. Groupe Français de Cytogénétique Hématologique (GFCH) (1991): t(10;11)(p13–14;q14–21): a new recurrent translocation in T-cell acute lymphoblastic leukemias. Genes Chromosom Cancer 3:411–415.
Figure 2 (A) Partial karyotype showing t(7;11)(q36;q13) in case 4 and (B) t(10;11)(p11.2;q13),del(11)(q23) in case 5. G-band with trypsin-Giemsa.
is a characteristic karyotypic aberration in MCL [20]. The PRAD1 (cyclin D1) locus has been identified in the 11q13 region [21], and the translocated 11q13 resulted in rearrangement of the PRAD1 gene, leading to overexpression of its transcript, the cell-cycle protein cyclin D1. However, none of the four cases examined immunohistochemically in this study showed cyclin D1 expression, suggesting that PRAD1 might not be involved in the pathogenesis of the leukemia despite the cytogenetic involvement of 11q13. The involvement of 11q13 in a diversity of chromosomal rearrangements in both myeloid and lymphoid neoplasia is intriguing. It is possible that a variety of breakpoints are involved in 11q13 abnormality which are indistinguishable at the microscopic level. On the other hand, the underlying molecular changes may be similar, despite the fact that different chromosomes are involved in rearrangement with 11q13, as in the case of 11q23 [22]. Further molecular study is required to clarify this. REFERENCES 1. Mitelman F, ed. (1991): Catalog of Chromosome Aberrations in Cancer, 4th Ed. Wiley-Liss, New York. 2. Thirman MJ, Gill HJ, Burnett RC, Mbangkollo D, McCabe NR, Kobayashi H, Ziemin-van der Poel S, Kaneko Y, Morgan R, Sandberg AA, Chaganti RSK, Larson RA, Le Beau MM, Diaz MO, Rowley JD (1993): Rearrangement of the MLL gene in
12. Brodeur GM, Williams DL, Kalwinsky DK, Williams KJ, Dahl GV (1983): Cytogenetic features of acute nonlymphoblastic leukemia in 73 children and adolescents. Cancer Genet Cytogenet 8:93–105. 13. Berger R, Flandrin G, Bernheim A, Le Coniat M, Vecchione D, Pacot A, Derré J, Daniel MT, Valensi F, Sigaux F, OchoaNoguera ME (1987): Cytogenetic studies on 519 consecutive de novo acute nonlymphocytic leukemias. Cancer Genet Cytogenet 29:9–21. 14. Raimondi SC, Kalwinsky DK, Hayashi Y, Behm FG, Mirro J Jr, Williams DL (1989): Cytogenetics of childhood acute nonlymphocytic leukemia. Cancer Genet Cytogenet 40:13–27. 15. Kaneko Y, Rowley JD, Variakojis D, Chilcote RR, Check I, Sakurai M (1982): Correlation of karyotype with clinical features in acute lymphobastic leukemia. Cancer Res 42:2918–2929. 16. Hayashi Y, Ohta Y, Kaneko Y, Sakurai M, Bessho F, Saito F (1985): 11;14 translocation in childhood T-cell acute lymphobastic leukemia. Jpn J Cancer Res 76:160–161. 17. Berger R, Le Coniat M, Derre J, Vecchione D, Chen SJ (1989): Chromosomal rearrangement on chromosome 11q14–q21 in T cell acute lymphobastic leukemia. Leukemia 3:560–562. 18. Huret JL, Heerema NA, Brizard A, Provisor AJ, Benz-Lemoine E, Guilhot F, Savage JRK, Tanzer J (1990): Two additional cases of t dic(9;12) in acute lymphocytic leukemia (ALL): prognosis in ALL with dic(9;12). Leukemia 4:423–425. 19. Heim S, Mitelman F, eds. (1987): Cancer Cytogenetics. Wiley-Liss, New York. pp. 85–87. 20. Raffeld M, Jaffe ES (1991): bcl-l, t(11;14), and mantle cell derived lymphomas. Blood 78:259–263. 21. Motokura T, Bloom T, Kim HG, Jupner H, Ruderman JV, Kronenberg HM, Arnold A (1991): A novel cyclin encoded by a bcl-1 linked candidate oncogenes. Nature 350:512–515. 22. Kwong YL, Tso SC, Wong KF, Tang JKC, Chan TK (1995): Translocational rearrangement of 11q23 in acute monoblastic leukemia. Cancer Genet Cytogenet 82:76–79.