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leukemia
Cancer Genetics and Cytogenetics 132 (2002) 81–82
Letter to the editor
Translocation (5;17)(q13;q21) in a case with precursor T-lymphoblastic lymphoma/leukemia
Acute lymphoblastic leukemia (ALL) is the most common leukemia in childhood. However, it comprises only 20% of acute leukemias in adults. The diagnosis of ALL is based on cell morphology, cytochemistry, and immunophenotype. These data together with cytogenetic features and expression of specific genes are required for optimal treatment planning [1]. In adults, higher white blood cell counts (30,000/l) and older age (60 years) represent adverse characteristics as these factors shorten durations of remissions and overall survival [2]. Other factors that have had some significance with certain treatment regimens are the percentage of circulating blast cells; the degree of bone marrow involvement; the presence of hepatomegaly, splenomegaly, or lymphadenopathy; central nervous system involvement at presentation; lactate dehydrogenase levels; and the time required to achieve complete remission [1]. Remarkably, cytogenetic studies play an important role in characterizing subsets of ALL with clinical differences. The most characteristic cytogenetic abnormalities are hyperdiploid karyotypes, t(9;22)(q34;q11), 11q23 (MLL gene) rearrangements, t(12;21)(p13;q22), t(1;19)(q23;p13) and t(8; 14)(q24;q32). In T-ALL, involvement of 14q11 band t(1; 14)(p31;q11), t(10;14)(q24;q11), t(8;14)(q24;q11) and del(1) (p32) are found. We report a 22-year-old woman who presented with neutropenia, extensive adenopathies, and splenomegaly in September 2000. Hematologic data showed Hb 107 g/dL, VCM 98 fl, WBC 1.8109/L with 2% neutrophils, 66% lymphocytes, 32% blast cells, and 145109/L platelets. A blastic infiltration of 57% was found in the bone marrow aspirate. Immunophenotyping of blasts cells showed positivity for TdT, CD2, CD3, CD5, CD7, CD34, CD117, CD123, CD13, and CD33. Cytogenetic study was performed on a 24-hour non-stimulated bone marrow culture following the standard procedures. Twenty metaphases were analysed on Gbanded slides and karyotype was described according to the ISCN 1995 nomenclature [3]. Thirteen cells showed the presence of a 45,XX,t(5;17)(q13;q21),10 karyotype (Fig. 1) and seven metaphases presented a normal 46,XX karyotype. An in situ hybridization was performed using the locus specific probe for the 17p13.1 region to rule out a 17p
anomaly involving the p53 region. A diagnosis of precursor T-lymphoblastic lymphoma/leukemia with myeloid markers was established and she started induction chemotherapy achieving cytologic and cytogenetic remission in October 2000. To our knowledge, this is the second reported case of T-lymphoblastic lymphoma/leukemia with a translocation (5;17)(q13;q21) [4,5]. The previous report did not focus on the mentioned translocation, as it was concerned with 17p anomalies in lymphoid malignancies. Neither of the two cases presented with t(5;17) as a sole aberration. In the present case, t(5;17) was found together with chromosome 10 monosomy. Monosomy of chromosome 10 has been described in T-ALL, always accompanied by other anomalies [6–8]. In contrast to the previously described case, our patient did not present p53 monosomy. It is worth mentioning that t(5;17), although affecting different breakpoints on chromosome 5 (5q13 vs. 5q35) but the same breakpoint on chromosome 17 (17q21), has been described in acute promyelocytic leukemia as a variant of the classical t(15; 17(q22;q21) [9]. In precursor T-ALL, the t(5;17)(q13;q21) represents a rare event. Clinical implications of this abnormality are unknown as well as its prognostic value. Acknowledgments The authors wish to thank Rosa Navarro, Rosa Ma Vilà, and Ma Carmen Vela for their excellent technical assistance.
0165-4608/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S0165-4608(01)00 5 2 3 - 4
Fig 1. Partial karyotype showing the translocation (5;17)(q13;q21).
82
L. Zamora et al. / Cancer Genetics and Cytogenetics 132 (2002) 81–82
Lourdes Zamora Blanca Espinet Francesc Solé Marta Salido Natàlia Rodon Lourdes Florensa Laboratori de Citologia Hematològica Laboratori de Referència de Catalunya Departament de Patologia Hospital del Mar Pg Marítim, 25-29, Barcelona 08003, Spain Soledad Woessner Escola de Citologia Hematològica S. Woessner-IMAS, Hospital del Mar IMAS, IMIM Barcelona, 08003, Spain
References [1] Larson RA, Stock W, Hoelzer DF, Kantarjian H. Acute lymphoblastic leukemia in adults. American Society of Hematology Educational Program Book, 1998. pp. 44–62.
[2] Larson RA, Doge RK, Burns CP, Lee EJ, Stone RM, Schulman P, Duggan D, Davey FR, Sobol RE, Frankel SR, Hooverman AL, Westbrook CA, Arthur DC, George SL, Bloomfield CD, Schiffer CA. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B Study 8811. Blood 1995;85:2025–37. [3] ISCN. An international system for human cytogenetic nomenclature. Mitelman F, editor. Basel: S. Karger, 1995. [4] Mitelman F. Catalog of chromosome aberrations in cancer. 6th ed. New York: Wiley-Liss Inc, 1998. [5] Schoch C, Rieder H, Stollmann-Gibbels B, Freund M, Tischler HJ, Silling-Engelhardt G, Fonatsch C. 17p anomalies in lymphoid malignancies: diagnostic and prognostic implications. Leuk Lymph 1995;17: 271–9. [6] Fujita K, Fukuhara S, Nasu K, Yamabe H, Tomono N, Inamoto Y, Shimazaki C, Ohno H, Doi S, Kamesaki H, Heshima Y, Uchino H. Recurrent chromosome abnormalities in adult T-cell lymphomas of peripheral T-cell origin. Int J Cancer 1986;37:517–24. [7] Fujita K, Yamasaki Y, Sawada H, Izumi Y, Fukuhara S, Uchino H. Cytogenetic studies on the adult T-cell leukemia in Japan. Leuk Res 1989;13:535–43. [8] Isobe M, Sadamori N, Russo G, Shimizu S, Yamamori S, Itoyama T, Yamada Y, Ikeda S, Ichimaru M, Kagan J, Croce CM. Rearrangements in the human T-cell-receptor alpha chain locus in patients with adult Tcell leukemia carrying translocations involving chromosome 14q11. Cancer Res 1990;50:6171–5. [9] Hummel JL, Wells RA, Dube ID, Licht JD, Kamel-Reid S. Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia. Oncogene 1999;18:633–41.
Letter to the editor
Translocation (5;17)(q13;q21) in a case with precursor T-lymphoblastic lymphoma/leukemia
Acute lymphoblastic leukemia (ALL) is the most common leukemia in childhood. However, it comprises only 20% of acute leukemias in adults. The diagnosis of ALL is based on cell morphology, cytochemistry, and immunophenotype. These data together with cytogenetic features and expression of specific genes are required for optimal treatment planning [1]. In adults, higher white blood cell counts (30,000/l) and older age (60 years) represent adverse characteristics as these factors shorten durations of remissions and overall survival [2]. Other factors that have had some significance with certain treatment regimens are the percentage of circulating blast cells; the degree of bone marrow involvement; the presence of hepatomegaly, splenomegaly, or lymphadenopathy; central nervous system involvement at presentation; lactate dehydrogenase levels; and the time required to achieve complete remission [1]. Remarkably, cytogenetic studies play an important role in characterizing subsets of ALL with clinical differences. The most characteristic cytogenetic abnormalities are hyperdiploid karyotypes, t(9;22)(q34;q11), 11q23 (MLL gene) rearrangements, t(12;21)(p13;q22), t(1;19)(q23;p13) and t(8; 14)(q24;q32). In T-ALL, involvement of 14q11 band t(1; 14)(p31;q11), t(10;14)(q24;q11), t(8;14)(q24;q11) and del(1) (p32) are found. We report a 22-year-old woman who presented with neutropenia, extensive adenopathies, and splenomegaly in September 2000. Hematologic data showed Hb 107 g/dL, VCM 98 fl, WBC 1.8109/L with 2% neutrophils, 66% lymphocytes, 32% blast cells, and 145109/L platelets. A blastic infiltration of 57% was found in the bone marrow aspirate. Immunophenotyping of blasts cells showed positivity for TdT, CD2, CD3, CD5, CD7, CD34, CD117, CD123, CD13, and CD33. Cytogenetic study was performed on a 24-hour non-stimulated bone marrow culture following the standard procedures. Twenty metaphases were analysed on Gbanded slides and karyotype was described according to the ISCN 1995 nomenclature [3]. Thirteen cells showed the presence of a 45,XX,t(5;17)(q13;q21),10 karyotype (Fig. 1) and seven metaphases presented a normal 46,XX karyotype. An in situ hybridization was performed using the locus specific probe for the 17p13.1 region to rule out a 17p
anomaly involving the p53 region. A diagnosis of precursor T-lymphoblastic lymphoma/leukemia with myeloid markers was established and she started induction chemotherapy achieving cytologic and cytogenetic remission in October 2000. To our knowledge, this is the second reported case of T-lymphoblastic lymphoma/leukemia with a translocation (5;17)(q13;q21) [4,5]. The previous report did not focus on the mentioned translocation, as it was concerned with 17p anomalies in lymphoid malignancies. Neither of the two cases presented with t(5;17) as a sole aberration. In the present case, t(5;17) was found together with chromosome 10 monosomy. Monosomy of chromosome 10 has been described in T-ALL, always accompanied by other anomalies [6–8]. In contrast to the previously described case, our patient did not present p53 monosomy. It is worth mentioning that t(5;17), although affecting different breakpoints on chromosome 5 (5q13 vs. 5q35) but the same breakpoint on chromosome 17 (17q21), has been described in acute promyelocytic leukemia as a variant of the classical t(15; 17(q22;q21) [9]. In precursor T-ALL, the t(5;17)(q13;q21) represents a rare event. Clinical implications of this abnormality are unknown as well as its prognostic value. Acknowledgments The authors wish to thank Rosa Navarro, Rosa Ma Vilà, and Ma Carmen Vela for their excellent technical assistance.
0165-4608/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S0165-4608(01)00 5 2 3 - 4
Fig 1. Partial karyotype showing the translocation (5;17)(q13;q21).
82
L. Zamora et al. / Cancer Genetics and Cytogenetics 132 (2002) 81–82
Lourdes Zamora Blanca Espinet Francesc Solé Marta Salido Natàlia Rodon Lourdes Florensa Laboratori de Citologia Hematològica Laboratori de Referència de Catalunya Departament de Patologia Hospital del Mar Pg Marítim, 25-29, Barcelona 08003, Spain Soledad Woessner Escola de Citologia Hematològica S. Woessner-IMAS, Hospital del Mar IMAS, IMIM Barcelona, 08003, Spain
References [1] Larson RA, Stock W, Hoelzer DF, Kantarjian H. Acute lymphoblastic leukemia in adults. American Society of Hematology Educational Program Book, 1998. pp. 44–62.
[2] Larson RA, Doge RK, Burns CP, Lee EJ, Stone RM, Schulman P, Duggan D, Davey FR, Sobol RE, Frankel SR, Hooverman AL, Westbrook CA, Arthur DC, George SL, Bloomfield CD, Schiffer CA. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B Study 8811. Blood 1995;85:2025–37. [3] ISCN. An international system for human cytogenetic nomenclature. Mitelman F, editor. Basel: S. Karger, 1995. [4] Mitelman F. Catalog of chromosome aberrations in cancer. 6th ed. New York: Wiley-Liss Inc, 1998. [5] Schoch C, Rieder H, Stollmann-Gibbels B, Freund M, Tischler HJ, Silling-Engelhardt G, Fonatsch C. 17p anomalies in lymphoid malignancies: diagnostic and prognostic implications. Leuk Lymph 1995;17: 271–9. [6] Fujita K, Fukuhara S, Nasu K, Yamabe H, Tomono N, Inamoto Y, Shimazaki C, Ohno H, Doi S, Kamesaki H, Heshima Y, Uchino H. Recurrent chromosome abnormalities in adult T-cell lymphomas of peripheral T-cell origin. Int J Cancer 1986;37:517–24. [7] Fujita K, Yamasaki Y, Sawada H, Izumi Y, Fukuhara S, Uchino H. Cytogenetic studies on the adult T-cell leukemia in Japan. Leuk Res 1989;13:535–43. [8] Isobe M, Sadamori N, Russo G, Shimizu S, Yamamori S, Itoyama T, Yamada Y, Ikeda S, Ichimaru M, Kagan J, Croce CM. Rearrangements in the human T-cell-receptor alpha chain locus in patients with adult Tcell leukemia carrying translocations involving chromosome 14q11. Cancer Res 1990;50:6171–5. [9] Hummel JL, Wells RA, Dube ID, Licht JD, Kamel-Reid S. Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia. Oncogene 1999;18:633–41.