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A new complex chromosomal translocation t(2;12;21)(q33;p13;q22) in B-cell acute lymphoblastic leukemia
Cancer Genetics and Cytogenetics 168 (2006) 179–180
Letter to the editor
A new complex chromosomal translocation t(2;12;21)(q33;p13;q22) in B-cell acute lymphoblastic leukemia The chromosomal t(12;21)(p13;q22) is present in approximately 25% of children with precursor-B acute lymphoblastic leukemia (ALL) and fuses genes ETV6 (alias TEL) and RUNX1 (alias AML1, CBFA2) [1]. Complex chromosomal translocations, involving three or more different chromosomes, have been observed in leukemia with t(9;22)(q34;q11.2), t(8;21)(q22;q22), t(15;17)(q22;q11), and rarely t(12;21)(p13;q22) [2]. We here describe a B-cell ALL case with a new complex translocation among chromosomes 2, 12, and 21. Physical examination of a 4-year-old girl in March 2004 revealed bony pain, large ganglia, and hepatosplenomegaly. Her peripheral blood values were hemoglobin 7.8 g/dL, leukocytes 4,100/mL with 82.4% lymphocytes, and platelets 24,000/mL. Bone marrow aspirate displayed blasts with L2 morphology, which were CD19, CD20, and CD22 positive. Chemotherapy consisting of vincristine, epirubicin, prednisone, and L-asparaginase was administered. At writing, the patient was in clinical and hematological remission with methotrexate as maintenance therapy.
Bone marrow cells were cultured and processed for chromosomal study. Karyotype description was according to ISCN 2005 [3]. The cultured cells displayed the karyotype 46,XX,t(2;12)(q33;p13)[2]/47,XX,t(2;12)(q33;p13),C21[2]/ 46,XX[12]. Fluorescence in situ hybridization with a commercial dual-color TEL/AML1 probe (Vysis, Downers Grove, IL) showed the fusion of these genes in all analyzed metaphase cells with the translocation (n Z 12). In contrast, cells without translocation did not show the fusion (n Z 15). The subclone with trisomy 21 and the fusion showed two independent red signals of AML1 equivalent to two normal chromosomes 21, plus a small extra red signal corresponding to 30 AML1 sequences on the derivative chromosome 2 (Fig. 1). Thus, we conclude the presence of a complex t(2;12;21)(q33;p13;q22). Complex translocations involving chromosomes 12, 21, and other chromosomes have been rarely reported. There are only 13 cases recorded in the Mitelman database of chromosome aberrations in cancer associated with ALL
Fig. 1. Fluorescence in situ hybridization with dual-color TEL (green) and AML1 (red) probe. Left: DAPI counterstained cell with the t(2;12) translocation and an apparent trisomy 21. Right: The same cell showing the TEL/AML1 gene fusion, two independent red signals, and an extra red signal corresponding to 30 AML1 sequences on the derivative chromosome 2. 0165-4608/06/$ – see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.cancergencyto.2005.12.012
180
Letter to the editor / Cancer Genetics and Cytogenetics 168 (2006) 179–180
[2]. On the other hand, there are 45 recorded translocations involving the chromosomal band 2q33 [2]. All these translocations are associated with leukemia or solid tumors, but only 10 of the 45 are present as the sole abnormality. Thus, this chromosomal band may contain one or more genes whose function could be important for initiation or progression of neoplasia. It has been proposed that complex translocations arise from two consecutive translocations [4,5]. Such an assumption agrees with the red signal remnant corresponding to the 30 AML1 region on the der(2) in this observation, a finding accounted for the translocation between chromosome 2 and the der(12). The prognostic significance of complex translocations is not clear, at least not for the complex translocations of the t(9;22)(q34;q11.2) with a sizeable number of cases [6]; the scarcity of patients with complex t(8;21) or t(15;17) translocations prevents a reliable conclusion [5]. The prognostic significance of the variant t(12;21)(p13;q22) remains to be determined, given that there are only 13 reported cases. These complex rearrangements may, however, contribute to tumoral progression by conferring some selective advantages to the clones containing them. Acknowledgments We thank Dr. Horacio Rivera for his critical review of the manuscript. E.A. Vasquez-Jimenez E.J. Romo-Martı´nez Divisio´n de Gene´tica CIBO-IMSS Guadalajara, Jalisco, Me´xico and Doctorado en Gene´tica Humana Universidad de Guadalajara Guadalajara, Jalisco, Mexico J.P. Meza-Espinoza Unidad Academica de Ciencias de la Salud y Tecnologı´a Facultad de Medicina de la Universidad
Autonoma de Tamaulipas Matamoros, Tamaulipas, Me´xico B. Lopez-Guido Departamento de Hematologia Hospital de Pediatria CMNO-IMSS Guadalajara, Jalisco, Me´xico M.T. Magan˜a-Torres J.R. Gonzalez-Garcia Divisio´n de Gene´tica CIBO-IMSS Sierra Mojada #800 Colonia Independencia CP 44340 Ap. Postal 1-3838 Guadalajara, Jalisco, Me´xico E-mail address: [email protected] (J.R. Gonzalez-Garcia)
References [1] Look AT. Oncogenic transcription factors in the human acute leukemias. Science 1997;278:1059–64. [2] Mitelman F, Johansson B, Mertens F, editors. Mitelman database of chromosome aberrations in cancer [Internet]. Available at: http://cgap. nci.nih.gov/Chromosomes/Mitelman. Updated November 22, 2005. Accessed December 19, 2005. [3] ISCN 2005: an international system for human cytogenetic nomenclature (2005). In: Shaffer LG, Tommerup N, editors. Basel: S. Karger, 2005. [4] Calabrese G, Stuppia L, Guanciali Franchi P, Peila R, Morizio E, Liberati AM, Spadano A, Di Lorenzo R, Donti E, Antonucci A, Palka G. Complex translocation of the Ph chromosome and Ph negative CML arise from similar mechanisms, as evidenced by FISH analysis. Cancer Genet Cytogenet 1994;78:153–9. [5] Calabrese G, Min T, Stuppia L, Powles R, Swansbury JG, Morizio E, Peila R, Donti E, Fioritoni G, Palka G. Complex chromosome translocations of standard t(8;21) and t(15;17) arise from a two-step mechanism as evidenced by fluorescence in situ hybridization analysis. Cancer Genet Cytogenet 1996;91:40–5. [6] Meza Espinoza JP, Picos Ca´rdenas VJ, Va´squez Jime´nez EA, Gutie´rrez Angulo M, Esparza Flores MA, Gonza´lez Garcı´a JR. A complex translocation (9;22;16)(q34;q11.2;p13) in chronic myelocytic leukemia. Cancer Genet Cytogenet 2005;157:175–7.
Letter to the editor
A new complex chromosomal translocation t(2;12;21)(q33;p13;q22) in B-cell acute lymphoblastic leukemia The chromosomal t(12;21)(p13;q22) is present in approximately 25% of children with precursor-B acute lymphoblastic leukemia (ALL) and fuses genes ETV6 (alias TEL) and RUNX1 (alias AML1, CBFA2) [1]. Complex chromosomal translocations, involving three or more different chromosomes, have been observed in leukemia with t(9;22)(q34;q11.2), t(8;21)(q22;q22), t(15;17)(q22;q11), and rarely t(12;21)(p13;q22) [2]. We here describe a B-cell ALL case with a new complex translocation among chromosomes 2, 12, and 21. Physical examination of a 4-year-old girl in March 2004 revealed bony pain, large ganglia, and hepatosplenomegaly. Her peripheral blood values were hemoglobin 7.8 g/dL, leukocytes 4,100/mL with 82.4% lymphocytes, and platelets 24,000/mL. Bone marrow aspirate displayed blasts with L2 morphology, which were CD19, CD20, and CD22 positive. Chemotherapy consisting of vincristine, epirubicin, prednisone, and L-asparaginase was administered. At writing, the patient was in clinical and hematological remission with methotrexate as maintenance therapy.
Bone marrow cells were cultured and processed for chromosomal study. Karyotype description was according to ISCN 2005 [3]. The cultured cells displayed the karyotype 46,XX,t(2;12)(q33;p13)[2]/47,XX,t(2;12)(q33;p13),C21[2]/ 46,XX[12]. Fluorescence in situ hybridization with a commercial dual-color TEL/AML1 probe (Vysis, Downers Grove, IL) showed the fusion of these genes in all analyzed metaphase cells with the translocation (n Z 12). In contrast, cells without translocation did not show the fusion (n Z 15). The subclone with trisomy 21 and the fusion showed two independent red signals of AML1 equivalent to two normal chromosomes 21, plus a small extra red signal corresponding to 30 AML1 sequences on the derivative chromosome 2 (Fig. 1). Thus, we conclude the presence of a complex t(2;12;21)(q33;p13;q22). Complex translocations involving chromosomes 12, 21, and other chromosomes have been rarely reported. There are only 13 cases recorded in the Mitelman database of chromosome aberrations in cancer associated with ALL
Fig. 1. Fluorescence in situ hybridization with dual-color TEL (green) and AML1 (red) probe. Left: DAPI counterstained cell with the t(2;12) translocation and an apparent trisomy 21. Right: The same cell showing the TEL/AML1 gene fusion, two independent red signals, and an extra red signal corresponding to 30 AML1 sequences on the derivative chromosome 2. 0165-4608/06/$ – see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.cancergencyto.2005.12.012
180
Letter to the editor / Cancer Genetics and Cytogenetics 168 (2006) 179–180
[2]. On the other hand, there are 45 recorded translocations involving the chromosomal band 2q33 [2]. All these translocations are associated with leukemia or solid tumors, but only 10 of the 45 are present as the sole abnormality. Thus, this chromosomal band may contain one or more genes whose function could be important for initiation or progression of neoplasia. It has been proposed that complex translocations arise from two consecutive translocations [4,5]. Such an assumption agrees with the red signal remnant corresponding to the 30 AML1 region on the der(2) in this observation, a finding accounted for the translocation between chromosome 2 and the der(12). The prognostic significance of complex translocations is not clear, at least not for the complex translocations of the t(9;22)(q34;q11.2) with a sizeable number of cases [6]; the scarcity of patients with complex t(8;21) or t(15;17) translocations prevents a reliable conclusion [5]. The prognostic significance of the variant t(12;21)(p13;q22) remains to be determined, given that there are only 13 reported cases. These complex rearrangements may, however, contribute to tumoral progression by conferring some selective advantages to the clones containing them. Acknowledgments We thank Dr. Horacio Rivera for his critical review of the manuscript. E.A. Vasquez-Jimenez E.J. Romo-Martı´nez Divisio´n de Gene´tica CIBO-IMSS Guadalajara, Jalisco, Me´xico and Doctorado en Gene´tica Humana Universidad de Guadalajara Guadalajara, Jalisco, Mexico J.P. Meza-Espinoza Unidad Academica de Ciencias de la Salud y Tecnologı´a Facultad de Medicina de la Universidad
Autonoma de Tamaulipas Matamoros, Tamaulipas, Me´xico B. Lopez-Guido Departamento de Hematologia Hospital de Pediatria CMNO-IMSS Guadalajara, Jalisco, Me´xico M.T. Magan˜a-Torres J.R. Gonzalez-Garcia Divisio´n de Gene´tica CIBO-IMSS Sierra Mojada #800 Colonia Independencia CP 44340 Ap. Postal 1-3838 Guadalajara, Jalisco, Me´xico E-mail address: [email protected] (J.R. Gonzalez-Garcia)
References [1] Look AT. Oncogenic transcription factors in the human acute leukemias. Science 1997;278:1059–64. [2] Mitelman F, Johansson B, Mertens F, editors. Mitelman database of chromosome aberrations in cancer [Internet]. Available at: http://cgap. nci.nih.gov/Chromosomes/Mitelman. Updated November 22, 2005. Accessed December 19, 2005. [3] ISCN 2005: an international system for human cytogenetic nomenclature (2005). In: Shaffer LG, Tommerup N, editors. Basel: S. Karger, 2005. [4] Calabrese G, Stuppia L, Guanciali Franchi P, Peila R, Morizio E, Liberati AM, Spadano A, Di Lorenzo R, Donti E, Antonucci A, Palka G. Complex translocation of the Ph chromosome and Ph negative CML arise from similar mechanisms, as evidenced by FISH analysis. Cancer Genet Cytogenet 1994;78:153–9. [5] Calabrese G, Min T, Stuppia L, Powles R, Swansbury JG, Morizio E, Peila R, Donti E, Fioritoni G, Palka G. Complex chromosome translocations of standard t(8;21) and t(15;17) arise from a two-step mechanism as evidenced by fluorescence in situ hybridization analysis. Cancer Genet Cytogenet 1996;91:40–5. [6] Meza Espinoza JP, Picos Ca´rdenas VJ, Va´squez Jime´nez EA, Gutie´rrez Angulo M, Esparza Flores MA, Gonza´lez Garcı´a JR. A complex translocation (9;22;16)(q34;q11.2;p13) in chronic myelocytic leukemia. Cancer Genet Cytogenet 2005;157:175–7.