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Kyo, Taichi
- Complex 8;21 Chromosome Translocations formed by Two Step Mechanism and Simple 8;21chromosome Translocation without AML1 Gene Involvement in Acute Myelocytic Leukemia
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Authors
Affiliations
1 Department of Radiobiology, Institute for Environmental Sciences, Takahoko 2-121, Rokkasho, Kamikita, Aomori 039- 3213, JP
2 Radiation Hazards Research Group, National Institute for Radiological Sciences, Anagawa 4-9-1, Chiba 263-8555, JP
3 Fourth Department of Internal Medicine, Hiroshima Red Cross Hospital, Senda-machi, 1-9-6, Minami-ku, Hiroshima 739-1743, JP
4 Hiroshima Atomic Bomb Relief Foundation, 50-1, 3 Chome Asakita-ku, Hiroshima 739-1743, JP
1 Department of Radiobiology, Institute for Environmental Sciences, Takahoko 2-121, Rokkasho, Kamikita, Aomori 039- 3213, JP
2 Radiation Hazards Research Group, National Institute for Radiological Sciences, Anagawa 4-9-1, Chiba 263-8555, JP
3 Fourth Department of Internal Medicine, Hiroshima Red Cross Hospital, Senda-machi, 1-9-6, Minami-ku, Hiroshima 739-1743, JP
4 Hiroshima Atomic Bomb Relief Foundation, 50-1, 3 Chome Asakita-ku, Hiroshima 739-1743, JP
Source
Indian Journal of Science and Technology, Vol 5, No 3 (2012), Pagination: 2240-2252Abstract
As a result of reciprocal translocation between chromosomes 8 and 21, acute myelocyticleukemia (AML) cells contains chimeric gene of AML1 and MTG8/ETO and express fusion proteins. The AML1-MTG8/ETO chimeric gene is considered to have an important role in the pathogenesis of AML FABM2. Among AML M2 patients, about 3 -5% of the patients show complex translocation including chromosome 8;21 and third chromosome. We analyzed metaphases from seven AML M2 patients with complex 8;21 translocation by two color FISH using WCP probes, AML1 probe and several cosmid probes locating near AML1 and MTG 8/ETO locus. All of the 7 patients could show two step translocation (chromosome8-chromosome 21-third chromosome). Seven patients including two insertion 8;21 cases represented two step translocation for formation either between chromosome [der(8); 8q-] and third chromosome or between [der(8); 8q-]and [der(21); 21q+ ] chromosomes . These results suggest that there is at least two step mechanism for the formation of complex 8;21 translocation, following formation of standard 8;21 translocation and AML1-MTG8/ETOchimeric gene. Interestingly, 3 patients diagnosed as AML FABM4, AML M2 transformed from myelodysplastic syndrome (MDS) (MDS-AMLM2) and acute lymphocytic leukemia (ALL) who had t(8;21) translocation had breakpoints proximal of AML1 gene. Other 13hematological disease such as AML or acute lymphocytic leukemia (ALL) patients who had chromosome abnormalities at band 21q22 of chromosome 21, including t(16;21)in 3 patients, had breakpoint at telomeric region of AML1. These results indicate that 21q22 chromosomal region has higher chromosome instability and is genetically extremely unstable.Keywords
Complex Chromosome Translocation, Acute Myelocytic Leukemia, Chromosome Instability, AML1, FISHFull Text
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Authors
Affiliations
1 Department of Radiobiology, Institute for Environmental Sciences, Hachazawa 2-121, Takahoko, Rokkasho, Kamikita, Aomori 019-3213, JP
2 Department of Cancer Cytogenetics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Minamiki-ku, Hiroshima 734-8552, JP
3 Radiation Hazards Research Group, National Institute for Radiological Sciences, Anagawa 4-9-1, Chiba 263-8555, JP
4 Fourth Department of Internal Medicine, Hiroshima Red Cross Hospital, Senda-machi, 1-9-6, Minami-ku, Hiroshima 739-1743, JP
5 Hiroshima Atomic Bomb Relief Foundation, 50-1, 3 Chome Asakita-ku, Hiroshima 739-1743, JP
1 Department of Radiobiology, Institute for Environmental Sciences, Hachazawa 2-121, Takahoko, Rokkasho, Kamikita, Aomori 019-3213, JP
2 Department of Cancer Cytogenetics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Minamiki-ku, Hiroshima 734-8552, JP
3 Radiation Hazards Research Group, National Institute for Radiological Sciences, Anagawa 4-9-1, Chiba 263-8555, JP
4 Fourth Department of Internal Medicine, Hiroshima Red Cross Hospital, Senda-machi, 1-9-6, Minami-ku, Hiroshima 739-1743, JP
5 Hiroshima Atomic Bomb Relief Foundation, 50-1, 3 Chome Asakita-ku, Hiroshima 739-1743, JP
Source
Indian Journal of Science and Technology, Vol 5, No 9 (2012), Pagination: 3229-3240Abstract
Acute myelocytic leukemia (AML), French-American-British (FAB) classification M3 contains variable clinical disease. About 90% of the AMLM3 has specific reciprocal chromosome translocation between chromosomes15 and 17, which resulted in PML-RARα and RARα-PML chimeric genes. We analyzed 39 AMLM3 patients who showed typical clinical M3 symptoms, with simple or complex 15;17 translocation or not, by metaphase and interphase fluorescence in situ hybridization (FISH) methods using both of PML-RARα and RARα-PML chimeric probes or reverse transcriptase PCR of PML-RARα chimeric gene. Thirty-one patients reported positive for PML-RARα gene while eight patients did not. Of interest, 6 of the 31 PML-RARα positive AMLM3 patients (19.4%) did not show RARα-PML chimeric signal, which was considered to be the cases having the deletion of the region locating RARα-PML chimeric gene on der (17) chromosome either after or at the same time of formation of simple 15;17 translocation. Out of 6, 2 patients had complex 15;17 translocation of t(3;15;17) and ins(15;17). Two-way translocation model might be more acceptable to show the mechanisms for formation of complex 15;17 translocation and insertion 15;17 where insertion of a region of chromosome 17 involving RARα into PML region of chromosome 15. These precise FISH analysis also revealed that AMLM3 acquired variable chromosomal instabilities such as deletion of RARα gene and segmental jumping translocation following 15;17 translocation and the FISH analysis will be applicable for classification of AMLM3.Keywords
15, 17 Chromosomal Translocation, Acute Myelocytic Leukemia (AML), Acute Promyelocytic Leukemia (APL), Chromosome Instability, PML, RARα, FISHFull Text
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Authors
Affiliations
1 Department of Radiobiology, Institute for Environmental Sciences, Takahoko 2-121, Rokkasho, Kamikita, Aomori 039-3213, JP
2 Department of Plant Biology & Plant Biotechnology, Presidency College, Chennai-600 005, IN
3 Department of Internal Medicine, Hiroshima Red Cross Hospital
4 Hiroshima Atomic Bomb Relief Foundation, 50-1, 3 Chome Asakita-ku, Hiroshima 739-1743, JP
1 Department of Radiobiology, Institute for Environmental Sciences, Takahoko 2-121, Rokkasho, Kamikita, Aomori 039-3213, JP
2 Department of Plant Biology & Plant Biotechnology, Presidency College, Chennai-600 005, IN
3 Department of Internal Medicine, Hiroshima Red Cross Hospital
4 Hiroshima Atomic Bomb Relief Foundation, 50-1, 3 Chome Asakita-ku, Hiroshima 739-1743, JP
Source
Indian Journal of Science and Technology, Vol 5, No 1 (2012), Pagination: 1801-1811Abstract
Importance of subtelomeric chromosome rearrangements associated with idiopathic mental retardation and with methylation of gene expression in neoplastic cells has been shown. In order to observe incidence of deletions or translocations involving subtelomere region in leukemias and lymphomas, 41 patients were observed precisely by chromosome metaphase fluorescent in situ hybridization (FISH) using subtelomere probes and so on, specially focus on the end of long arm of chromosome 11 or short arm of chromosome 17. The abnormalities of subtelomere region on chromosome 11 were frequently observed in 7 of 17 patients (41.6%) with 11q22-q25 abnormalities, which were 3 of 9 patients with add(11)(q23-q25) and 3 of 7 patients with del(11)(q22-25), and 16 of 24 patients (66.0%) with 17p13 abnormalities, which were 2 of 6 with translocation between 17 and other chromosome, 6 of 10 with add(17)(p13) and all of 8 with del(17)(p13). Lymphoid disease had slightly higher abnormalities of subtelomere region than myeloid disease in patients with 11q22-25 or 17p13 abnormalities. Chemo- or radiotherapy treated patients had also subtelomeric chromosomal rearrangements. These results indicate that leukemia and lymphomas have many abnormalities at subtelomere region and possible association of chromosome instability, relating to pathogenesis of these diseases especially after therapy. Furthermore, FISH and chromosome analyses were performed on long-term cultured HL-60 leukemic cell line after irradiation using three different sources, and the results confirmed the higher induction of chromosome instability involving subtelomere region after α-rays irradiation.Keywords
Chromosome Instability, Subtelomere, Telomere, Radiation, α-rays, γ-rays, β-rays, Leukemia Cell Line, FishAnalysisFull Text
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