- Email: [email protected]
Translocation (1;3)(p36;q21) at relapse in a child with acute myeloid leukemia and normal karyotype at diagnosis
Cancer Genetics and Cytogenetics 191 (2009) 59e61
Letter to the editor
Translocation (1;3)(p36;q21) at relapse in a child with acute myeloid leukemia and normal karyotype at diagnosis We present a 6-year-old girl with acute myeloid leukemia (AML)-M5, normal karyotype at the time of diagnosis, and t(1;3)(p36;q21) at relapse. The t(1;3)(p36;q21) is a rare but recurrent chromosomal aberration in human malignancies that it is primary observed in adults but is extremely rare in children. To the best of our knowledge, only one child with MDS and t(1;3)(p36;q21) has been reported in the literature so far. Our case is the second report of this translocation in a child. According to the first report, the t(1;3) was not observed at diagnosis, but was found after chemotherapy and adds new evidence of an association between t(1;3) and previous exposure to cytotoxic agents. The t(1;3)(p36;q21) was observed in patients with myelodysplastic syndrome (MDS) [1e8], acute myeloid leukemia [9e14], essential thrombocythemia [15], chronic myelomonocytic leukemia [16], and sideroblastic anemia [17]. Two genes have been recently identified near the translocation breakpoints d the MEL1 gene at 1q36.3 and the RPN1 gene at 3q21 [18,19]. Investigations of translocation breakpoints and gene expression, however, gave variable results and the molecular mechanism involved in leukemogenesis has not yet been determined [20e22]. Most observations described in the literature involve adult patients. The aberration is rare in children and has not been observed in a child with acute leukaemia. Here, we present the cytogenetic and clinical data of a child with acute myeloid leukemia who showed a normal karyotype at diagnosis and t(1;3)(p36;q21) at relapse. Our patient was referred to the hospital because of headache, temperature, weakness, and abdominal pain. A blood analysis showed a hemoglobin level of 112 g/L, a white blood cell (WBC) count of 17.8 109/L (polymorphonuclear 2%, lymphocytes 2%, blasts 93%), and a platelet count of 73 109/L. The diagnosis of AML-M5 was made according to FrencheAmericaneBritish classification [23]. Chemotherapy with a combination of cytosine arabinoside, rubomycin, and VP-16 was initiated, resulting in complete remission. Despite maintenance chemotherapy and prophylactic central nervous system irradiation, relapse occurred. Re-induction chemotherapy was successful, resulting in a second remission followed by the preparation for bone marrow transplantation. Treatment with high doses of cytosine 0165-4608/09/$ e see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.cancergencyto.2009.01.014
arabinoside was started. The patient’s clinical condition deteriorated, however, and the second relapse occurred, followed by short recovery and then a third relapse. A blood analysis showed a haemoglobin level of 95 g/L, a WBC count of 6.5 109/L (polymorphonuclears 2%, lymphocytes 6%, monocytes 6%, blasts 65%), and a platelet count of 100 109/L. The patient did not respond to therapy and died 19 months after the initial diagnosis. Cytogenetic analysis was performed on two occasions. The investigation was carried out at the time of diagnosis (before initiating therapy) and at the third relapse. Slides were obtained by 24-hour bone marrow cell culture without mitogen stimulation. The GTG-banding method for chromosome identification was used. Chromosomal abnormalities were described in accordance with the ISCN suggestions [24]. Nineteen metaphases had been analyzed at diagnosis and no clonal chromosome aberrations were observed. The modal karyotype was 46,XX. Additional cytogenetic analysis was performed at the third relapse. Normal karyotype was detected in 18 (41.9 %) and clonal chromosome aberrations in 25 (58.1%) out of 43 metaphases. The t(1;3)(p36;q21) was identified in each of 25 abnormal metaphases. In 14 (32.6%) cells, translocation was present as the sole abnormality. In 11 (25.6%) metaphases, besides t(1;3), the structural rearrangement of chromosome 14 was identified (Fig. 1). An aberrant chromosome 14 presented additional material of unknown origin attached at the end of the long arm, add(14)(q32). Since the first description of t(1;3)(p36;q21) some 47 cases have been reported so far, including 18 (38%) with myelodisplastic syndrome [1e8,15,19,21,22], 8 (17%) with de novo acute myeloid leukemia [9e15], and 12 (26%) with AML occurring after MDS [8,19,25e31]. The aberration was reported in all subtypes of AML, but most frequently in AML-M4. The t(1;3)(p36;q21) is rare in children. To our knowledge, only one juvenile patient has been reported with this translocation: Moir et al. described a 14-year-old girl with MDS and t(1;3) observed at diagnosis, before therapy was started [5]. In contrast, our patient is a 6-year-old girl with AML-M5 presenting normal karyotype at diagnosis and t(1;3) at relapse. The significance of the appearance of the abnormal clone at relapse is unclear and the subject of scientific discussion. Different mechanisms of the
60
Letter to the editor / Cancer Genetics and Cytogenetics 191 (2009) 59e61
treatment for leukemia and the appearance of t(1;3) at relapse.
Acknowledgments This work was supported by grant from Ministry of Science, Education and Sports in the Republic of Croatia (Project no. 072-1083107-0361). Iskra Petkovic´ Department of Medical Genetics Children’s Hospital Zagreb University of Zagreb Medical School Klaic´eva 16 10000 Zagreb, Croatia E-mail address: [email protected] (I. Petkovic´) Mirna Anicic´ Department of Pediatrics University of Zagreb Medical School Sˇalata Y, 10000 Zagreb, Croatia
Fig. 1. Partial karyotype showing translocation t(1;3)(p36;q21) and add(14)(q32).
emergence of abnormal clone at relapse have been suggested. This may result from a failure to detect chromosomal aberration at diagnosis, the presence of a subclone derived from the cytogenetically normal preleukemic stem cell, or the clonal abnormality at relapse may be related to a previous exposure to mutagens [32,33]. The t(1;3) in our patient was detected at the third relapse and after exposure to cytotoxic agents used in the treatment of leukemia. Results of cytogenetic analysis support the possibility of a causal relationship between chemotherapy and the occurrence of t(1;3) in our child with acute leukemia. In fact, literature data have revealed that the t(1;3)(p36;q21) was found in 6/47 patients (12.8%) upon diagnosis of acute leukemia secondary to chemotherapy/ radiotherapy for breast cancer, Hodgkin’s disease, multiple myeloma, polycithemia vera, and in one case of essential thrombocythaemia treated with 32P [9,15,31,34e37]. The t(1;3) was identified as a sole anomaly in 3/7 cases, and additional chromosomal aberrations were observed in 4/7 cases (57.1%), including our patient. Deletion of the long arm of chromosome 5 was reported in two patients and monosomy 7 in one patient [9,35,36]. On the other hand, our patient presented structural rearrangement of the long arm of chromosome 14 and evidence of clonal evolution, which were not reported in the patient with t(1;3), and secondary leukemia so far. The interval between cytotoxic exposure and t(1;3) appearance ranged from 28 to 108 months. In contrast to previous reports, in our patient with de novo AML, the t(1;3) emerged during disease treatment and was detected only at relapse, 17 months from the first cytotoxic exposure. This investigation adds new evidence for an association of t(1;3) with previous exposure to cytotoxic agents. In this study, we present additional data on a rare but recurrent aberration in the patient with AML. This is the second case of t(1;3)(p36;q21) in a child, and the first report suggesting relationship between chemotherapy
Melita Nakic´ Laboratory of Hematology Children’s Hospital Zagreb University of Zagreb Medical School Klaic´eva 16 10000 Zagreb, Croatia Josip Konja Department of Pediatrics University of Zagreb Medical School Sˇalata Y, 10000 Zagreb, Croatia References [1] Varga AE. Clustering of 1p36 breakpoints distal to 1p36.2 in haematological malignancies. Cancer Genet Cytogenet 2001;125:78e9. [2] Wieser R, Schreiner U, Pirc-Danoewinata H, Aytekin M, Schidt HH, Rieder H, Fonatsch C. Interphase fuorescent in situ hybridization assay for detection of 3q21 rearrangements in myeloid malignancies. Genes Chromosomes Cancer 2001;32:373e80. [3] Larripa I, Labal de Vinuesa M, Bengio R, Slavutsky. Chromosome studies in Human Hematologic diseases: II Myelodysplastic syndrome. Haematologica 1987;72:399e403. [4] Mautitzson N, Johansson B, Rylander L, Albin M, Stromberg U, Billstrom R, Ahlgren T, Mikoczy Z, Mitelman F, Hagmar L, Nilsson PG. The prognostic impact of karyotypic subgroups in myelodysplastic syndromes is strongly modified by sex. Br J Haematol 2001;113:347e456. [5] Moir DJ, Jones PAE, Pearson J, Duncan JR, Cook P, Buckle VJ. A new translocation, t(1;3)(p36;q21), in myelodysplastic disorders. Blood 1984;64:553e5. [6] Rios Gonzalez A, Salazar J, Moraleda JM, del Canizo MC. Translocation (1;3) in myelodysplastic disorders. Blood 1985;65:509e10. [7] Xinh PT, Tri KN, Nagao H, Nakazato H, Taketazu F, Fujisawa S, Yagasaki F, Chen ZY, Hayashi Y, Toyoda A, Hattori M, Sakaki Y, Tokunaga K, Sato Y. Breakpoints at 1p36.3 in three MDS/AML (M4) patients with t(1;3) (p36;q21) occur in the first intron and in
Letter to the editor / Cancer Genetics and Cytogenetics 191 (2009) 59e61
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16] [17]
[18]
[19]
[20]
[21]
the 5’ region of MEL 1. Genes Chromosomes Cancer 2003;36: 313e6. Vigue F, Marie JP, Poler F, Bernadou A. Three cases of preleukemic myelodysplastic disorders with the same translocation t(1;3). Cancer Genet Cytogenet 1986;19:213e8. Bloomfield CD, Garson MO, Volin L, Knuutila S, De la Chapelle A. (1;3)(p36;q21) in acute nonlymphocytic leukaemia: a new cytogenetic- clinicopathologic association. Blood 1985;66:1409e13. Sato Y, Murai M, Tsunoda J, Komatsu N, Muroi K, Yoshida M, Motoyoshi K, Sakamoto S, Miura Y. Second relapse of acute promyelocytic leukaemia (ANLL-M3) with t(15;17) and t(1;3)(p36;q21). Cancer Genet Cytogenet 1991;57:53e8. Atichatakarn V, Punyammalee B, Wongsasant B, Jootar S. Acute Nonlymphocytic leukaemia with a translocation (1;3)(p36;q21) in an XYY man. Cancer genet Cytogenet 1986;21:79e83. Grigg AP, Gascoyne RD, Phillios GL, Horsman DE. Clinical, haematological and cytogenetic features in 24 patients with structural rearrangements of the q arm of chromosome 3. Br J Haematol 1993;83: 158e65. Poirel H, Radford-Weiss I, Rack K, Troussard X, Veil A, Valensi F, Picard F, Guesnu M, Leboeuf D, Melle J, Dreyfus F, Flandrin G, Macintyre E. Detection of the chromosome 16 CBFb-MYH11 fusion transcript in myelomonocytic leukemias. Blood 1995;85: 1313e22. Wieser R, Volz A, Schnittger S, Jager U, Gruner H, Meran JG, Wimmer K, Ziegler A, Fonatsch C. Mapping of leukaemia-associated breakpoints in chromosome band 3q21 using a new established PAC contig. Br J Haematol 2000;110:343e50. Secker-Walker LM, Mehta A, Bain B. Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study. Br J Haematol 1995;91:490e501. Iselius L, Hast R, Ost A, Kinell C. Translocation t(1;3)(p36;q21) in chronic myelomonocytic leukaemia. Br J Haematol 1989;72:109e10. Fukuoka T, Kameoka H, Yasukawa M, Yanagisawa K, Tamai T. Translocation (1;3)(p36;q21) in sideroblastic anaemia. Acta Haemat 1989;82:146e9. Mochizuki N, Shimizu S, Nagasawa T, Tanaka H, Taniwaki M, Yokota J, Morishita K. A novel gene, MEL 1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transciptionally activated in t(1;3)(p36;q21)-positive leukaemia cells. Blood 2000; 36:3209e14. Shimizu S, Suzukawa K, Kodera T, Nagasawa T, Abe T, Taniwaki M, Yagasaki F, Tanaka H, Fujisawa S, Johansson B, Ahlgren T, Yokota J, Morishita K. Identification of breakpoint cluster regions at 1p36.3 and 3q21 in malignancies with t(1;3)(p36;q21). Genes Chromosomes Cancer 2000;27:229e38. Nashikata I, Sasaki H, Iga M, Tateno Y, Imayoshi S, Asou N, Nakamura T, Morishita K. A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36:q21)positive AML and blocks G-CSF-induced myeloid differentiation. Blood 2003;102:3323e32. Xiao Z, Zhang M, Liu X, Zhang Y, Yang L, Hao Y. MEL1S, not Mel 1, is overexpressed in myelodysplastic syndromes patients with t(1;3)(p36;q21). Leukemia Res 2006;30:332e4.
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[22] Lahortiga I, Agirre X, Belloni E, Vazquez I, Larrayoz MJ, Gasparini P, Lo Coco F, Pelicci PG, Calasanz MJ, Odero MD. Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is widely expressed in normal tissue, including bone marrow, and it is not overexpressed in the t(1;3) cells. Oncogene 2004;23:311e6. [23] Bennett JM, Carovsky D, Daniel MT, Flandrin G, Galton DAG, Grelnick HR, Sulton G. Proposals for the classification of the acute leukemias. Br J Haematol 1976;33:451e8. [24] ISCN. An International System for Human Cytogenetic Nomenclature. In: Shaffer LG, Tommerup N, editors. Basel: S Karger, 2005. [25] Olah E, Balogh E, Kovacs I, Kiss A. Abnormalities of chromosome 1 in relation to human malignant diseases. Cancer Genet Cytogenet 1989;43:179e94. [26] Charrin C, Belhabri A, Treille-Ritouet D, Theuil G, Magaud JP, Fiere D. Thomas Xavier. Structural rearrangements of chromosome 3 in 57 patients with acute myeloid leukaemia: clinical, haematological and cytogenetic features. Hematol J 2002;3:21e31. [27] Welborn JL, Lewis JP, Jenks H, Walling P. Diagnostic and prognostic significance of t(1;3)(p35;q21) in the disorders of hematopoiesis. Cancer Genet Cytogenet 1987;28:277e85. [28] Group Francais de Cytogenetique Hematologique (GFCH). Cytogenetic analysis in patients with primary myelodysplastic syndromes in leukemic transformation. A report on 94 cases. Hematol Cell Ther 1996;38:177e81. [29] Marsden KA, Pearse AM, Collins GG, Ford DS, Heard S, Kimber RI. Acute leukaemia with t(1;3)(p36;q21), evolution to t(1;3)(p36;q21), t(14;17)(q32;q21), and loss of red cell A and Leb antigens. Cancer Genet Cytogenet 1992;64:80e5. [30] Scheres JMJC, Hustinx TWJ, Haasjes JG, Haanen C. Specific translocation t(1;3) in acute myelomonocytic leukaemia: a further case. Cancer Genet Cytogenet 1986;22:69e73. [31] Cambrin GR, Mecucci C, Van Orshoven A, Tricot G, Van den Berghe H. Translocation (1;3)(p36;q21) in malignant myeloid stem cell disorders. Cancer Genet Cytogenet 1986;22:75e81. [32] Raimondi CS, Pui CH, Head DR, Rivera GK, Behm FG. Cytogenetically different leukemic clones at relapse of childhood acute lymphoblastic leukemia. Blood 1993;82:576e80. [33] Walker H, Smith FJ, Betts DR. Cytogenetics in acute myeloid leukaemia. Blood Rev 1994;8:30e6. [34] Cuneo A, Van Orshoven A, Michaux JL, Boogaerts M, Louwagie A, Doyen Ch, Dal Cin P, Fagioli F, Castoldi G, Van den Berghe H. Morphologic, immunologic and cytogenetic studies in erythroleukaemia: evidence for multilineage involvement and identification of two distinct cytogenetic-clinicopathological types. Br J Haematol 1990; 75:346e54. [35] Panani AD, Ferti-Passantonopoulou A, Economopoulos T, Raptis S. Translocation (1;3)(p36;q21) in secondary leukaemia. Cancer Genet Cytogenet 1990;50:165e7. [36] Berger R, Bernheim A, Flandrin G, Dresch C, Najean Y. Cytogenetic studies on acute nonlymphocytic leukemias following polycythemia vera. Cancer Genet Cytogenet 1984;11:441e51. [37] Najfeld V, Coyle T, Berk PD. Transformation of polycythemia vera to acute nonlymphocytic leukaemia accompanied by t(1,39(p36;q21) karyotype. Cancer Genet Cytogenet 1988;33:193e200.
Letter to the editor
Translocation (1;3)(p36;q21) at relapse in a child with acute myeloid leukemia and normal karyotype at diagnosis We present a 6-year-old girl with acute myeloid leukemia (AML)-M5, normal karyotype at the time of diagnosis, and t(1;3)(p36;q21) at relapse. The t(1;3)(p36;q21) is a rare but recurrent chromosomal aberration in human malignancies that it is primary observed in adults but is extremely rare in children. To the best of our knowledge, only one child with MDS and t(1;3)(p36;q21) has been reported in the literature so far. Our case is the second report of this translocation in a child. According to the first report, the t(1;3) was not observed at diagnosis, but was found after chemotherapy and adds new evidence of an association between t(1;3) and previous exposure to cytotoxic agents. The t(1;3)(p36;q21) was observed in patients with myelodysplastic syndrome (MDS) [1e8], acute myeloid leukemia [9e14], essential thrombocythemia [15], chronic myelomonocytic leukemia [16], and sideroblastic anemia [17]. Two genes have been recently identified near the translocation breakpoints d the MEL1 gene at 1q36.3 and the RPN1 gene at 3q21 [18,19]. Investigations of translocation breakpoints and gene expression, however, gave variable results and the molecular mechanism involved in leukemogenesis has not yet been determined [20e22]. Most observations described in the literature involve adult patients. The aberration is rare in children and has not been observed in a child with acute leukaemia. Here, we present the cytogenetic and clinical data of a child with acute myeloid leukemia who showed a normal karyotype at diagnosis and t(1;3)(p36;q21) at relapse. Our patient was referred to the hospital because of headache, temperature, weakness, and abdominal pain. A blood analysis showed a hemoglobin level of 112 g/L, a white blood cell (WBC) count of 17.8 109/L (polymorphonuclear 2%, lymphocytes 2%, blasts 93%), and a platelet count of 73 109/L. The diagnosis of AML-M5 was made according to FrencheAmericaneBritish classification [23]. Chemotherapy with a combination of cytosine arabinoside, rubomycin, and VP-16 was initiated, resulting in complete remission. Despite maintenance chemotherapy and prophylactic central nervous system irradiation, relapse occurred. Re-induction chemotherapy was successful, resulting in a second remission followed by the preparation for bone marrow transplantation. Treatment with high doses of cytosine 0165-4608/09/$ e see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.cancergencyto.2009.01.014
arabinoside was started. The patient’s clinical condition deteriorated, however, and the second relapse occurred, followed by short recovery and then a third relapse. A blood analysis showed a haemoglobin level of 95 g/L, a WBC count of 6.5 109/L (polymorphonuclears 2%, lymphocytes 6%, monocytes 6%, blasts 65%), and a platelet count of 100 109/L. The patient did not respond to therapy and died 19 months after the initial diagnosis. Cytogenetic analysis was performed on two occasions. The investigation was carried out at the time of diagnosis (before initiating therapy) and at the third relapse. Slides were obtained by 24-hour bone marrow cell culture without mitogen stimulation. The GTG-banding method for chromosome identification was used. Chromosomal abnormalities were described in accordance with the ISCN suggestions [24]. Nineteen metaphases had been analyzed at diagnosis and no clonal chromosome aberrations were observed. The modal karyotype was 46,XX. Additional cytogenetic analysis was performed at the third relapse. Normal karyotype was detected in 18 (41.9 %) and clonal chromosome aberrations in 25 (58.1%) out of 43 metaphases. The t(1;3)(p36;q21) was identified in each of 25 abnormal metaphases. In 14 (32.6%) cells, translocation was present as the sole abnormality. In 11 (25.6%) metaphases, besides t(1;3), the structural rearrangement of chromosome 14 was identified (Fig. 1). An aberrant chromosome 14 presented additional material of unknown origin attached at the end of the long arm, add(14)(q32). Since the first description of t(1;3)(p36;q21) some 47 cases have been reported so far, including 18 (38%) with myelodisplastic syndrome [1e8,15,19,21,22], 8 (17%) with de novo acute myeloid leukemia [9e15], and 12 (26%) with AML occurring after MDS [8,19,25e31]. The aberration was reported in all subtypes of AML, but most frequently in AML-M4. The t(1;3)(p36;q21) is rare in children. To our knowledge, only one juvenile patient has been reported with this translocation: Moir et al. described a 14-year-old girl with MDS and t(1;3) observed at diagnosis, before therapy was started [5]. In contrast, our patient is a 6-year-old girl with AML-M5 presenting normal karyotype at diagnosis and t(1;3) at relapse. The significance of the appearance of the abnormal clone at relapse is unclear and the subject of scientific discussion. Different mechanisms of the
60
Letter to the editor / Cancer Genetics and Cytogenetics 191 (2009) 59e61
treatment for leukemia and the appearance of t(1;3) at relapse.
Acknowledgments This work was supported by grant from Ministry of Science, Education and Sports in the Republic of Croatia (Project no. 072-1083107-0361). Iskra Petkovic´ Department of Medical Genetics Children’s Hospital Zagreb University of Zagreb Medical School Klaic´eva 16 10000 Zagreb, Croatia E-mail address: [email protected] (I. Petkovic´) Mirna Anicic´ Department of Pediatrics University of Zagreb Medical School Sˇalata Y, 10000 Zagreb, Croatia
Fig. 1. Partial karyotype showing translocation t(1;3)(p36;q21) and add(14)(q32).
emergence of abnormal clone at relapse have been suggested. This may result from a failure to detect chromosomal aberration at diagnosis, the presence of a subclone derived from the cytogenetically normal preleukemic stem cell, or the clonal abnormality at relapse may be related to a previous exposure to mutagens [32,33]. The t(1;3) in our patient was detected at the third relapse and after exposure to cytotoxic agents used in the treatment of leukemia. Results of cytogenetic analysis support the possibility of a causal relationship between chemotherapy and the occurrence of t(1;3) in our child with acute leukemia. In fact, literature data have revealed that the t(1;3)(p36;q21) was found in 6/47 patients (12.8%) upon diagnosis of acute leukemia secondary to chemotherapy/ radiotherapy for breast cancer, Hodgkin’s disease, multiple myeloma, polycithemia vera, and in one case of essential thrombocythaemia treated with 32P [9,15,31,34e37]. The t(1;3) was identified as a sole anomaly in 3/7 cases, and additional chromosomal aberrations were observed in 4/7 cases (57.1%), including our patient. Deletion of the long arm of chromosome 5 was reported in two patients and monosomy 7 in one patient [9,35,36]. On the other hand, our patient presented structural rearrangement of the long arm of chromosome 14 and evidence of clonal evolution, which were not reported in the patient with t(1;3), and secondary leukemia so far. The interval between cytotoxic exposure and t(1;3) appearance ranged from 28 to 108 months. In contrast to previous reports, in our patient with de novo AML, the t(1;3) emerged during disease treatment and was detected only at relapse, 17 months from the first cytotoxic exposure. This investigation adds new evidence for an association of t(1;3) with previous exposure to cytotoxic agents. In this study, we present additional data on a rare but recurrent aberration in the patient with AML. This is the second case of t(1;3)(p36;q21) in a child, and the first report suggesting relationship between chemotherapy
Melita Nakic´ Laboratory of Hematology Children’s Hospital Zagreb University of Zagreb Medical School Klaic´eva 16 10000 Zagreb, Croatia Josip Konja Department of Pediatrics University of Zagreb Medical School Sˇalata Y, 10000 Zagreb, Croatia References [1] Varga AE. Clustering of 1p36 breakpoints distal to 1p36.2 in haematological malignancies. Cancer Genet Cytogenet 2001;125:78e9. [2] Wieser R, Schreiner U, Pirc-Danoewinata H, Aytekin M, Schidt HH, Rieder H, Fonatsch C. Interphase fuorescent in situ hybridization assay for detection of 3q21 rearrangements in myeloid malignancies. Genes Chromosomes Cancer 2001;32:373e80. [3] Larripa I, Labal de Vinuesa M, Bengio R, Slavutsky. Chromosome studies in Human Hematologic diseases: II Myelodysplastic syndrome. Haematologica 1987;72:399e403. [4] Mautitzson N, Johansson B, Rylander L, Albin M, Stromberg U, Billstrom R, Ahlgren T, Mikoczy Z, Mitelman F, Hagmar L, Nilsson PG. The prognostic impact of karyotypic subgroups in myelodysplastic syndromes is strongly modified by sex. Br J Haematol 2001;113:347e456. [5] Moir DJ, Jones PAE, Pearson J, Duncan JR, Cook P, Buckle VJ. A new translocation, t(1;3)(p36;q21), in myelodysplastic disorders. Blood 1984;64:553e5. [6] Rios Gonzalez A, Salazar J, Moraleda JM, del Canizo MC. Translocation (1;3) in myelodysplastic disorders. Blood 1985;65:509e10. [7] Xinh PT, Tri KN, Nagao H, Nakazato H, Taketazu F, Fujisawa S, Yagasaki F, Chen ZY, Hayashi Y, Toyoda A, Hattori M, Sakaki Y, Tokunaga K, Sato Y. Breakpoints at 1p36.3 in three MDS/AML (M4) patients with t(1;3) (p36;q21) occur in the first intron and in
Letter to the editor / Cancer Genetics and Cytogenetics 191 (2009) 59e61
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16] [17]
[18]
[19]
[20]
[21]
the 5’ region of MEL 1. Genes Chromosomes Cancer 2003;36: 313e6. Vigue F, Marie JP, Poler F, Bernadou A. Three cases of preleukemic myelodysplastic disorders with the same translocation t(1;3). Cancer Genet Cytogenet 1986;19:213e8. Bloomfield CD, Garson MO, Volin L, Knuutila S, De la Chapelle A. (1;3)(p36;q21) in acute nonlymphocytic leukaemia: a new cytogenetic- clinicopathologic association. Blood 1985;66:1409e13. Sato Y, Murai M, Tsunoda J, Komatsu N, Muroi K, Yoshida M, Motoyoshi K, Sakamoto S, Miura Y. Second relapse of acute promyelocytic leukaemia (ANLL-M3) with t(15;17) and t(1;3)(p36;q21). Cancer Genet Cytogenet 1991;57:53e8. Atichatakarn V, Punyammalee B, Wongsasant B, Jootar S. Acute Nonlymphocytic leukaemia with a translocation (1;3)(p36;q21) in an XYY man. Cancer genet Cytogenet 1986;21:79e83. Grigg AP, Gascoyne RD, Phillios GL, Horsman DE. Clinical, haematological and cytogenetic features in 24 patients with structural rearrangements of the q arm of chromosome 3. Br J Haematol 1993;83: 158e65. Poirel H, Radford-Weiss I, Rack K, Troussard X, Veil A, Valensi F, Picard F, Guesnu M, Leboeuf D, Melle J, Dreyfus F, Flandrin G, Macintyre E. Detection of the chromosome 16 CBFb-MYH11 fusion transcript in myelomonocytic leukemias. Blood 1995;85: 1313e22. Wieser R, Volz A, Schnittger S, Jager U, Gruner H, Meran JG, Wimmer K, Ziegler A, Fonatsch C. Mapping of leukaemia-associated breakpoints in chromosome band 3q21 using a new established PAC contig. Br J Haematol 2000;110:343e50. Secker-Walker LM, Mehta A, Bain B. Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study. Br J Haematol 1995;91:490e501. Iselius L, Hast R, Ost A, Kinell C. Translocation t(1;3)(p36;q21) in chronic myelomonocytic leukaemia. Br J Haematol 1989;72:109e10. Fukuoka T, Kameoka H, Yasukawa M, Yanagisawa K, Tamai T. Translocation (1;3)(p36;q21) in sideroblastic anaemia. Acta Haemat 1989;82:146e9. Mochizuki N, Shimizu S, Nagasawa T, Tanaka H, Taniwaki M, Yokota J, Morishita K. A novel gene, MEL 1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transciptionally activated in t(1;3)(p36;q21)-positive leukaemia cells. Blood 2000; 36:3209e14. Shimizu S, Suzukawa K, Kodera T, Nagasawa T, Abe T, Taniwaki M, Yagasaki F, Tanaka H, Fujisawa S, Johansson B, Ahlgren T, Yokota J, Morishita K. Identification of breakpoint cluster regions at 1p36.3 and 3q21 in malignancies with t(1;3)(p36;q21). Genes Chromosomes Cancer 2000;27:229e38. Nashikata I, Sasaki H, Iga M, Tateno Y, Imayoshi S, Asou N, Nakamura T, Morishita K. A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36:q21)positive AML and blocks G-CSF-induced myeloid differentiation. Blood 2003;102:3323e32. Xiao Z, Zhang M, Liu X, Zhang Y, Yang L, Hao Y. MEL1S, not Mel 1, is overexpressed in myelodysplastic syndromes patients with t(1;3)(p36;q21). Leukemia Res 2006;30:332e4.
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[22] Lahortiga I, Agirre X, Belloni E, Vazquez I, Larrayoz MJ, Gasparini P, Lo Coco F, Pelicci PG, Calasanz MJ, Odero MD. Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is widely expressed in normal tissue, including bone marrow, and it is not overexpressed in the t(1;3) cells. Oncogene 2004;23:311e6. [23] Bennett JM, Carovsky D, Daniel MT, Flandrin G, Galton DAG, Grelnick HR, Sulton G. Proposals for the classification of the acute leukemias. Br J Haematol 1976;33:451e8. [24] ISCN. An International System for Human Cytogenetic Nomenclature. In: Shaffer LG, Tommerup N, editors. Basel: S Karger, 2005. [25] Olah E, Balogh E, Kovacs I, Kiss A. Abnormalities of chromosome 1 in relation to human malignant diseases. Cancer Genet Cytogenet 1989;43:179e94. [26] Charrin C, Belhabri A, Treille-Ritouet D, Theuil G, Magaud JP, Fiere D. Thomas Xavier. Structural rearrangements of chromosome 3 in 57 patients with acute myeloid leukaemia: clinical, haematological and cytogenetic features. Hematol J 2002;3:21e31. [27] Welborn JL, Lewis JP, Jenks H, Walling P. Diagnostic and prognostic significance of t(1;3)(p35;q21) in the disorders of hematopoiesis. Cancer Genet Cytogenet 1987;28:277e85. [28] Group Francais de Cytogenetique Hematologique (GFCH). Cytogenetic analysis in patients with primary myelodysplastic syndromes in leukemic transformation. A report on 94 cases. Hematol Cell Ther 1996;38:177e81. [29] Marsden KA, Pearse AM, Collins GG, Ford DS, Heard S, Kimber RI. Acute leukaemia with t(1;3)(p36;q21), evolution to t(1;3)(p36;q21), t(14;17)(q32;q21), and loss of red cell A and Leb antigens. Cancer Genet Cytogenet 1992;64:80e5. [30] Scheres JMJC, Hustinx TWJ, Haasjes JG, Haanen C. Specific translocation t(1;3) in acute myelomonocytic leukaemia: a further case. Cancer Genet Cytogenet 1986;22:69e73. [31] Cambrin GR, Mecucci C, Van Orshoven A, Tricot G, Van den Berghe H. Translocation (1;3)(p36;q21) in malignant myeloid stem cell disorders. Cancer Genet Cytogenet 1986;22:75e81. [32] Raimondi CS, Pui CH, Head DR, Rivera GK, Behm FG. Cytogenetically different leukemic clones at relapse of childhood acute lymphoblastic leukemia. Blood 1993;82:576e80. [33] Walker H, Smith FJ, Betts DR. Cytogenetics in acute myeloid leukaemia. Blood Rev 1994;8:30e6. [34] Cuneo A, Van Orshoven A, Michaux JL, Boogaerts M, Louwagie A, Doyen Ch, Dal Cin P, Fagioli F, Castoldi G, Van den Berghe H. Morphologic, immunologic and cytogenetic studies in erythroleukaemia: evidence for multilineage involvement and identification of two distinct cytogenetic-clinicopathological types. Br J Haematol 1990; 75:346e54. [35] Panani AD, Ferti-Passantonopoulou A, Economopoulos T, Raptis S. Translocation (1;3)(p36;q21) in secondary leukaemia. Cancer Genet Cytogenet 1990;50:165e7. [36] Berger R, Bernheim A, Flandrin G, Dresch C, Najean Y. Cytogenetic studies on acute nonlymphocytic leukemias following polycythemia vera. Cancer Genet Cytogenet 1984;11:441e51. [37] Najfeld V, Coyle T, Berk PD. Transformation of polycythemia vera to acute nonlymphocytic leukaemia accompanied by t(1,39(p36;q21) karyotype. Cancer Genet Cytogenet 1988;33:193e200.