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ATL発症高危険群の長期追跡と発病予防の検討

Research Project

Project/Area Number 12218104
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNational Institute of Infectious Diseases (2004)
Kumamoto University (2000-2003)

Principal Investigator

山口 一成  国立感染症研究所, 血液・安全性研究部, 部長 (20128325)

Co-Investigator(Kenkyū-buntansha) 日野 茂男  鳥取大学, 医学部, 教授 (70012763)
石田 尚臣  東京大学, 医科学研究所, 助手 (80293447)
上平 憲  長崎大学, 医学部, 教授 (80108290)
望月 學  東京医科歯科大学, 大学院, 教授 (10010464)
出雲 周二  鹿児島大学, 医学部, 教授 (30143811)
渡辺 俊樹 (渡邊 俊樹)  東京大学, 医科学研究所, 助教授 (30182934)
片峰 茂  長崎大学, 医学部, 教授 (40161062)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥120,600,000 (Direct Cost: ¥120,600,000)
Fiscal Year 2004: ¥23,800,000 (Direct Cost: ¥23,800,000)
Fiscal Year 2003: ¥24,800,000 (Direct Cost: ¥24,800,000)
Fiscal Year 2002: ¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 2001: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 2000: ¥23,000,000 (Direct Cost: ¥23,000,000)
KeywordsATL / HTLV-I / HTLV-Iキャリア / HTLV-Iぶどう膜炎 / HAM / 潜伏感染 / HTLV-I ぶどう膜炎 / コホート研究 / HTLV-Iキャリアの長期フォロー / HTLV-Iプロウイルス量 / HAE / HTLV-I母子感染
Research Abstract

キャリアの中からATL発症のハイリスクグループを絞り込み、年間発症率が約5%になる群を対象として、発症予防の臨床介入を試みるために、九州、四国、関東でのキャリア登録、検体の収集を3年前から開始している(JSPFADプロジェクト)。臨床情報と末梢血でのプロウイルス量、sIL-2R、HLAなどとの関連についてデータを集積中である。JSPFADからいくつかの他のプロジェクトにも臨床検体が供給されている。
1.遺伝子プロフィリング解析:DNAアレイ解析により腫瘍化と進展を特徴付ける遺伝子群を明らかにし、発症危険群の同定と分子標的療法をめざす。約1万遺伝子のクラスター解析の結果、活性化正常Tリンパ球と細胞株、HTLV-I感染と非感染のT細胞株、感染T細胞株内で、ATL由来細胞とin vitroでの不死化細胞のそれぞれが別のクラスターに、ATL細胞も独自のクラスターに分類される。腫瘍細胞の特徴的プロファイルを明らかにすることで、腫瘍化に関与する遺伝子群の解明が可能になる。
2.ATLに対する分子標的療法:新規NF-kB阻害剤(DHMEQ)は、in vitro及びSCIDマウスを用いた研究で、特異的にATL細胞、HTLV-I感染細胞のアポトーシスを誘導し、キャリアの末梢血の感染細胞数を減少させた。発症予防を含めた、臨床応用にむけて準備を進めている。

Report

(5 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (25 results)

All 2005 2004 Other

All Journal Article (6 results) Publications (19 results)

  • [Journal Article] Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker for acute-type adult T-cell leukemia.2005

    • Author(s)
      Sasaki H. et al.
    • Journal Title

      Blood 105(3)

      Pages: 1204-13

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Sensitivity of adult T-cell leukaemia lymphoma cells to tumour necrosis factor-related apoptosis-inducing ligand.2005

    • Author(s)
      Hasegawa H. et al.
    • Journal Title

      Br J Haematol 128(2)

      Pages: 253-65

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Role of HTLV-1 proviral DNA load and clonality in the development of adult T-Cell leukemia/Lymphoma in asymptomatic carriers.2004

    • Author(s)
      Okayama A. et al.
    • Journal Title

      Int J Cancer 110

      Pages: 621-625

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Decreased human T lymphotropic virus type I (HTLV-I) provirus load and alteration in T cell phenotype after interferon-alpha therapy for HTLV-I-associated myelopathy/tropical spastic paraparesis.2004

    • Author(s)
      Saito M. et al.
    • Journal Title

      J Infect Dis 137

      Pages: 29-40

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Rapid tumor death model for evaluation of new therapeutic agents for Adult T-cell Leukemia.2004

    • Author(s)
      Ohsugi T. et al.
    • Journal Title

      Lab.Invest 84

      Pages: 263-266

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clinical and oncologic implications in epigenetic down-regulation of CD26/dipeptidyl peptidase IV in adult T-cell leukemia cells.2004

    • Author(s)
      Tsuji T. et al.
    • Journal Title

      Int J Hematol 80(3)

      Pages: 254-260

    • Related Report
      2004 Annual Research Report
  • [Publications] Yamaguchi K.et al.: "Detection"(2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koiwa T, Watanabe T. et al.: "5'-long terminal repeat-selective CpG methylation of latent human T-cell leukemia virus type 1 provirus in vitro and in vivo"J.Virology. 76. 9389-9397 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogata M, Kikuchi H, et al.: "Successful bone marrow transplantation from an unrelated donor in a patient with adult T-cell leukemia"Bone Marrow Transplantation. 30(10). 699-701. (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iga, M., Okayama, A., et al.: "Genetic evidence of transmission of human T-lymphotropic virus type-I between spouses"J.Infect.Dis. 185. 691-695 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takemoto S, Taguchi H. et al.: "Dendritic cells and adult T-cell leukemia/lymphoma"Annals of Oncology.. 13. 106 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoh, M., Yamaguchi, K.et al.: "Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4 + 25 + HTLV-1-infected T-cells in human carriers of both HTLV-1 and S.stercoralis"Oncogene. 21. 2466-2475 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Umehara F, Izumo S, et al.: "Involvement of Fas/Fas ligand system in the spinal cords of HTLV-I-associated myelopathy"Acta Neuropathol. 103(4). 384-390 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamauchi K.他9名(2番目): "Sequential change of virus markers in seroconverters with community-acquired infection of human T lymphotropic virus type I"J Infect Dis.. 183. 1031-1037 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watanabe T.他7名(5番目): "Deletion of the pl6ink4a gene in ex vivo acute ATLL cells and methylation of pl6ink4a promotor in HTLV-I-infected T-cell lines"AIDS Res Hum Retrovirus. 16. 709-713 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kamihira S.他9名(9番目): "Vascular endothelial growth factor and cellular chemotaxis : a possible autocrine pathway in adult T-cell leukemia cell invasion"Clin. Cancer Res.. Sep.7・9. 2719-2726 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Izumo S.他4名(4番目): "Existence of escape mutant in HTLV-I tax during thedevelopment of adult T-cell leukemia"Blood. 97・4. 987-993 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taguchi H.他4名(5番目): "Lactate dehydrogenase production and release in newly establishd human myeloma cell line"Am J Hematol. 66. 267-273 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hasegawa H.他5名(4番目): "High production of interferon-gamma but not interleukin-2 by human T cell lymphotropic virus typeI (HTLV-I)-infected peripheral blood mononuclear cells"Blood. 98. 721-726 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Nakayama,S.Kamihira, et al.: "Expression and phosphorylation status of retinoblastoma protein in adult T-cell leukemia/lymphoma."Leukemia Research. 24. 299-305 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Kamihira,N.Dateki, et al.: "Keat-time polymerase chain reaction for quantification of HTLV-1 proviral load : Application for analyzing aberrant integration of the proviral DNA in adult T-cell leukemia."Int J Hematol. 72. 79-84 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Tanggo,K.Yamaguchi, et al.: "Human T lymphotropic virus I in Indonesia."Intervirology. 43. 77-79 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] C Boschi-Pinto,A Okayama, et al.: "A follow-up study of morbidity and mortality associated with hepatitis C virus infection and its interaction with human T lymphotropic virus type I in Miyazaki Japan"J.Inf.D.. 18. 35-41 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Trovato R, Watanabe T, et al,: "Deletion of the p16INK4A gene in ex vivo acute ATLL cells and methylation of p16INK4A promoter in HTLV-I-infected T-cell lines."AIDS research and Human Retroviruses. 16. 709-713 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Furukawa Y,Izumo S, et al.: "Phylogenetic subtypes of HTLV-I gene and their risk to HTLV-I-assiciated myelopathy."J Infect Dis.. 182. 1343-1349 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2018-03-28  

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