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セミパラチンスク旧ソ連実験場周辺の骨髄異形成症候群(MDS)・白血病の分子疫学

Research Project

Project/Area Number 21406001
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Risk sciences of radiation/Chemicals
Research InstitutionHiroshima University

Principal Investigator

木村 昭郎  Hiroshima University, 原爆放射線医科学研究所, 教授 (70127645)

Co-Investigator(Kenkyū-buntansha) 兵頭 英出夫  広島大学, 原爆放射線医科学研究所, 准教授 (30253074)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2011: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2010: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2009: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywordsセミパラチンスク / 骨髄異形成症候群 / 白血病 / 放射線 / AML1/RUNX1 / MDS / セミバラチンス / AML1
Research Abstract

セミパラチンスク旧ソ連核実験場周辺住民の被曝様式は、広島の被爆様式とはまったく異なっていることから、悪性腫瘍の発生様式も異なっている可能性がある。本研究では、セミパラチンスク核実験場周辺住民のMDS・白血病の症例数をさらに増加させ分子遺伝学的特徴を明らかにする。特にAML1/RUNX1遺伝子変異、及びAML1/RUNX1変異と協調してMDS・白血病発症に関与していると考えられるN-RAS,SHP-2,NF1,FLT3の遺伝子変異、さらにP53変異について解析する。次に被曝線量を導入して、線量、性別、被曝時年齢等の効果について原爆被爆者との比較を行い、被爆様式の違いによる差異を明らかにすることを目的としている。そこでセミパラチンスク市のカザフ放射線医学環境研究所、市診断センター、市救急病院と連携して、セミパラチンスク核実験場周辺住民のMDS・白血病症例のスライド標本と患者情報収集を継続している。一方原爆被爆者のMSD・白血病については、MDS/白血病(芽球が5%以上認められるMDSと三血球系統の異形成を伴った白血病が含まれる)の遺伝子解析が進んでいる。最近集計したMDS/白血病248例にしめるAML1/RUNX1点変異陽性率は、原爆被爆者13/36(36%)に対して非被爆者35/212(17%)と、被爆者では有意に高頻度であった。このことからAML1/RUNX1の点変異は放射線誘発のMDS/白血病にかなり特徴的な遺伝子変異であることが明らかになった。この点からはセミパラチンスク周辺の被ばく住民と広島の原爆被爆者では被爆様式は異なっているが、MDS/白血病を発症する主要な分子遺伝学的メカニズムは共通していると言える。

Report

(2 results)
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (21 results)

All 2010 2009

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (10 results) Book (1 results)

  • [Journal Article] Roles of Src-like adaptor protein 2 (SLAP-2) in GPVI-mediated platelet activation SLAP-2 and GPVI signaling.2010

    • Author(s)
      Sugihara S., et al
    • Journal Title

      Thrombosis Research

      Volume: 126

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Giant granulocytic sarcoma of the vagina concurrent with acute myeloid leukemia with t(9;21)(q22;q22) translocation.2010

    • Author(s)
      Imagawa J., et al
    • Journal Title

      International Journal of Hematology

      Volume: 92 Pages: 553-555

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expansion of CD8^+/perforin^+ effector memory T cells in the bone marrow of patients with thymoma-associated pure red cell aplasia.2010

    • Author(s)
      Nitta H., et al
    • Journal Title

      British Journal of Haematology

      Volume: 150 Pages: 712-715

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and genetic features of therapy-related myeloid neoplasms after chemotherapy for acute promyelocytic leukemia.2010

    • Author(s)
      Imagawa J., et al
    • Journal Title

      Blood

      Volume: 116 Pages: 6018-6022

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 1.治療関連骨髄異形成症候群(MDS)/白血病の疾患概念の疫学.特集・治療関連骨髄異形成症候群(MDS)/白血病2010

    • Author(s)
      木村昭郎
    • Journal Title

      血液フロンティア

      Volume: 20 Pages: 21-29

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms2009

    • Author(s)
      Ding Y, et al
    • Journal Title

      Blood 114

      Pages: 5201-5205

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lenalidomide is active in Japanese patients with symptomatic anemia in low- or intermediate-1 risk myelodysplastic syndromes with a deletion 5q abnormality2009

    • Author(s)
      Harada H, et al
    • Journal Title

      International Journal of Hematology 90

      Pages: 353-360

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BMI-1 expression is enhanced through transcriptional and posttrans criptional regulation during the progression of chronic myeloid leukemia2009

    • Author(s)
      Bhattacharyya J, et al
    • Journal Title

      Ann Hematol 88

      Pages: 333-340

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated T-cell-mediated immunotherapy with a chimeric receptor against CD38 in B-cell non-Hodgkin lymphoma2009

    • Author(s)
      Mihara K, et al
    • Journal Title

      J Immunother. 32

      Pages: 737-743

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acquired pure red cell aplasia associated with malignant lymphomas : a nationwide cohort study in Japan for the PRCA Collaborative Study Group2009

    • Author(s)
      Hirokawa M, et al
    • Journal Title

      Am J Hematol. 84

      Pages: 144-148

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] B-cell lymphoma cells overexpressing BMI-1 are correlated with drug resistance through enhanced expression of survivin and are effectively eliminated by T cells with anti-CD38 chimeric receptor.2010

    • Author(s)
      Bhattacharyya, J., et al
    • Organizer
      52^<th> Annual Meeting of the American Society of Hematology
    • Place of Presentation
      New Orleans
    • Year and Date
      2010-12-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] Expansion of CD8^+/perforin^+ effector memory T cells in the bone marrow with thymoma-associated PRCA.2010

    • Author(s)
      Nitta, H., et al
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] BMI-1 is correlated with drug resistance in B-cell lymphomas through enhanced expression of survivin.2010

    • Author(s)
      Bhattacharyya, J., et al
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular mechanisms to produce MDS/AML by C-terminal trancated type of AML1/RUNX1 mutations.2010

    • Author(s)
      Harada, H., et al
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨髄増殖性腫瘍からの白血病移行メカニズムの解明2010

    • Author(s)
      丁曄, 他
    • Organizer
      第107回日本内科学会講演会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Six Month Treatment of Low Dose Eltrombopag Is Efficatcious in Japanese Patients with Refractory Chronic Immune Thrombocytopenic Purpura (ITP)2009

    • Author(s)
      Tomiyama Y, et al
    • Organizer
      51^<th> Annual Meeting of the American Society of Hematology
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2009-12-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] AML1/RUNX1 Point Mutation Possibly Promotes Leukemic Transformation in Myeloproliferative Disorders2009

    • Author(s)
      Imagawa J, et al
    • Organizer
      51^<th> Annual Meeting of the American Society of Hematology
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2009-12-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] Levels of sIL-2R in Sera Depend On Number of CD25-Positive Lymphoma Cells and MMP-9-Positive Macrophages in DLBCL2009

    • Author(s)
      Yoshida N, et al
    • Organizer
      51^<th> Annual Meeting of the American Society of Hematology
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2009-12-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] BMI-1 and AML-1 Point Mutation in the Pathogenesis of MDS2009

    • Author(s)
      Kimura A
    • Organizer
      10^<th> International Symposium on Myelodysplastic Syndromes
    • Place of Presentation
      パトラ Greece
    • Year and Date
      2009-05-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] Results of Phase II Clinical Study of Leunalidomide in Japanese Patients with Myelodysplastic Syndrome (MDS)2009

    • Author(s)
      Harada H, et al
    • Organizer
      10^<th> International Symposium on Myelodysplastic Syndromes
    • Place of Presentation
      パトラ Greece
    • Year and Date
      2009-05-07
    • Related Report
      2009 Annual Research Report
  • [Book] 血液疾患診療ハンドブック2009

    • Author(s)
      田中英夫, 木村昭郎
    • Total Pages
      671
    • Publisher
      医薬ジャーナル社
    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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