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2001 Fiscal Year Final Research Report Summary

Epidemiological and molecular biological study of myelodysplastic syndrome (MDS) among atomic bomb survivors

Research Project

Project/Area Number 11480141
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 環境影響評価(含放射線生物学)
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

KIMURA Akiro  Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射能医学研究所, 教授 (70127645)

Co-Investigator(Kenkyū-buntansha) TANAKA Hideo  Hiroshima University, Research Institute for Radiation Biology and Medicine, Associate Professor, 原爆放射能医学研究所, 助教授 (50243613)
HAYAKAWA Norihiko  Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射能医学研究所, 教授 (40022834)
Project Period (FY) 1999 – 2001
KeywordsMDS / Atomic bomb / Radiation / AML 1 / DNA repair / 放射線 / 被爆
Research Abstract

To study the effect of radiation exposure on MDS development among Hiroshima A bomb survivors, patients with definite individual radiation dose were examined between 1985 and 1999. The dose was estimated according to ABS 93 dosimetry system. Among 735 patients without malignancy, 26 patients aged from 48 to 88 (median : 75) had diagnosis of MDS, including 16 RA, 2 RARS, 4 RAEB and 4 RAEBt. We analyzed the relative risk in relation to exposed radiation dose using a multiple regression with Cox proportional hazard model. Highly significant dose-effect on the risk of MDS was found. The relative risk was 2.53 (95 % CI : 1.49-4.30) at the dose of 100 cSv against 0 cSv (P = 0.0006). Age at the time of bombing showed significant effects on the risk (P = 0.0000). This is the first time that the incidence of hematological disease other than leukemia was found to be radiation dose dependent.
In order to clarify the molecular mechanism of A bomb radiation-induced MDS/AML, we studied the mutations of AML 1 which plays important roles in the definitive hematopoiesis by forming the transcription factor complex with CBF β. We have analyzed the DNA-binding domain (the runt domain) of AML 1 gene for mutations by PCR-SSCP assay using genomic DNA from bone marrow samples followed by sequence analysis. AML 1 mutations were identified in 46 % (6/13) of A bomb radiation-exposed MDS patients. Two cases had silent mutations (P157syn and T101syn), 3 cases had missense mutations (G42R, D171N and G42R), and one case had a frame shift/nonsense mutation (L70del 1bp to stop). In addition, missense mutations were found in 2/3 radiotherapy-related MDS/AML patients. On the other hand, AML 1 mutations were found in only 2.9 % (2/70) of sporadic MDS cases. The high incidence of AML 1 gene mutations in radiation-associated MDS/AML suggested that dysregulation of AML 1 function plays pivotal roles in this category of hematopoietic disorders.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] 木村昭郎: "骨髄異形成症候群(MDS)「血液・造血器疾患・免疫機構の障害」"日本臨床 本邦臨床統計集(1). 59(増刊号7). 504-544 (2001)

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  • [Publications] Harada, Y. et al.: "A hematopoietic-specific transmembrane protein, Art-1, is possibly requlated by AML1"Biochem.Bioph.Res.Com.. 284(3). 714-722 (2001)

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  • [Publications] Kimura, A. et al.: "Atomic bomb radiation enhances the risk of MDS"Leukemia Research. 25(Suppl). S13 (2001)

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  • [Publications] Harada, Y. et al.: "Somatic mutations of the AML1 gene are frequent in therapyrelated and rediation-associated myelodysplastic syndrome/acute myeloid leukemia(MDS/AML)"Blood. 98(11). 567a (2001)

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  • [Publications] 蔵本 憲 他: "放射線リスクの高い血液疾患:骨髄異形成症候群"放射線生物研究. (印刷中). (2001)

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  • [Publications] Ban, S.et al.: "Radiosensitivity and expression of nucleotide excision repair genes in peripheral blood mononuclear cells of myelodysplastic syndrome patients"Int.Congress Series. 730(in press). (2001)

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  • [Publications] 木村昭郎: "インフォームドコンセントガイダンス-血液疾患診療編-"先端医学社. 493 (2001)

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  • [Publications] Harigae, H., et al.: "A novel mutation of the erythroid-specific δ -aminolaevulinate synthase gene in a patient with X-linked sideroblastic anaemia"Br. J. Haematol.. 106. 175-177 (1999)

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  • [Publications] Harigae, H et al.: "Two novel mutations of the 5 δ -aminolaevulinate synthase-2 gene in innherited and non-inherited sideroblastic anemia"Blood. 94. 191a (1999)

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  • [Publications] Kuramoto, K., et al.: "ZK7, a novel zinc finger gene, is induced by vascular endothelial growth factor and inhibits apoptotic death in hematopoietic cells"Cancer Res.. 60. 425-430 (2000)

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  • [Publications] Kimura, A., et al.: "Strong radiation effect for myelodysplastic syndrome (MDS) among atomic bomb survivors"Int. J. Hematol. 72. 110 (2000)

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  • [Publications] Oguma, N., et al.: "Various response patterns of Ph1 cells to IFN-α in patients with chronic myelocytic leukemia"Exp. Oncol.. 22. 73-77 (2000)

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  • [Publications] Fujii, T., et al.: "A new approach to detect reticulated platelets stained with thiazole orange in thrombocytopenic patients"Thrombo. Res.. 97. 431-440 (2000)

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  • [Publications] Nobuyoshi, M., et al.: "Arrest human dendritic cells at the CD34-/CD4+/HLA-DR+ stage in the bone marrow of NOD/SCID-human chimeric mice"Blood. 97. 3655-3657 (2001)

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  • [Publications] Tanaka, H., et al.: "Acute myelogenous leukemia with PIG-A gene mutation evolved from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome"Int. J. Hematol. 73. 206-212 (2001)

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Published: 2003-09-17  

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