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Clinical significance of cytotoxic factor-mediated graft-versus-leukemia effect against high-risk childhood leukemia

Research Project

Project/Area Number 21591356
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionUniversity of Yamanashi

Principal Investigator

INUKAI Takeshi  山梨大学, 大学院・医学工学総合研究部, 准教授 (30293450)

Co-Investigator(Renkei-kenkyūsha) AKAHANE Koshi  山梨大学, 医学部・附属病院, 助教 (90377531)
HIROSE Kinuko  山梨大学, 大学院・医学工学総合研究部, 医学研究員 (70436880)
KURODA Itaru  山梨大学, 大学院・医学工学総合研究部, 医学研究員 (30402051)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords白血病 / 造血幹細胞移植 / 移植片対白血病効果 / TRAIL / 細胞傷害因子 / 小胞体ストレス / BCR-ABL
Research Abstract

Graft-versus-leukemia(GVL) effect after allogeneic stem cell transplantation can potentially eradicate residual disease in high risk childhood acute lymphoblastic leukemia patients. TRAIL, which is one of cytotoxic factors expressed on cytotoxic T-cells and natural killer cells, is known to play a role in the GVL effect by inducing apoptotic cell death of leukemia cells through death receptors expression on leukemia cells. In the present study, we demonstrated that oncogenic fusion products derived from chromosomal translocations sensitized leukemia cells to TRAIL-mediated apoptosis by upregulating death receptor expression in t(17 ; 19) and Philadelphia chromosome-positive leukemia.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (28 results)

All 2011 2010 2009 Other

All Journal Article (14 results) (of which Peer Reviewed: 12 results) Presentation (6 results) Remarks (8 results)

  • [Journal Article] Endoplasmic reticulum stress inducers, but not imatinib, sensitize Philadelphia chromosome-positive leukemia cells to TRAIL-mediated apoptosis2011

    • Author(s)
      Zhang X, Inukai T, Akahane K, Hirose K, Kuroda I, et al
    • Journal Title

      Leuk Res

      Volume: 35 Pages: 940-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Successful tandem (autologous-cord blood) SCT in advanced neuroblastomas with highly amplified MYCN2011

    • Author(s)
      Goi K, Inukai T, et al
    • Journal Title

      Bone Marrow Transplant

      Volume: 46 Issue: 4 Pages: 835-839

    • DOI

      10.1111/j.1365-2141.2011.08965.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endoplasmic reticulum stress inducers, but not imatinib, sensitize Philadelphia chromosome-positive leukemia cells to TRAIL-mediated apoptosis2011

    • Author(s)
      Zhang X, Inukai T, et al
    • Journal Title

      Leuk Ees.

      Volume: 35 Issue: 7 Pages: 940-949

    • DOI

      10.1016/j.leukres.2011.03.016

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of cancer stem cell properties by CD9 in human B-acute lymphoblastic leukemia2011

    • Author(s)
      Yamazaki H, Inukai T, et al
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 409 Issue: 1 Pages: 14-21

    • DOI

      10.1016/j.bbrc.2011.04.098

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Resistance of T-cell acute lymphoblastic leukemia totumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis2010

    • Author(s)
      Akahane K, Inukai T, Hirose K, Kuroda I, et al
    • Journal Title

      Exp Hematol

      Volume: 38 Pages: 885-95

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Resistance of T-cell acute lymphoblastic leukemia to tumor necrosis fact or-related apoptosis-inducing ligand-mediated apoptosis.2010

    • Author(s)
      Akahane K
    • Journal Title

      Exp Hematol.

      Volume: 38 Pages: 885-895

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A specific linkage between the incidence of TP53 mutations and type of chromosomal translocations in B-precursor acute lymphoblastic leukemia cell lines.2010

    • Author(s)
      Inukai T
    • Journal Title

      Am J Hematol.

      Volume: 85 Pages: 535-537

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17 ; 19).2010

    • Author(s)
      Hirose K
    • Journal Title

      Blood

      Volume: 116 Pages: 962-970

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leucemia, 1984-1999.2010

    • Author(s)
      Tsuchida M, ら
    • Journal Title

      Leukemia 24

      Pages: 383-396

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 小児難治性白血病の細胞傷害因子TRAILに対する感受性の意義(総説)2009

    • Author(s)
      犬飼岳史
    • Journal Title

      日本小児血液学会雑

      Volume: 23 Pages: 332-344

    • Related Report
      2011 Final Research Report
  • [Journal Article] 小児難治性白血病の細胞傷害因子TRAILに対する感受性の意義2009

    • Author(s)
      犬飼岳史
    • Journal Title

      日本小児血液学会雑誌 23

      Pages: 332-344

    • NAID

      10029311164

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Long-term survival after HLA-haploidentical SCT from noninherited maternal antign-mismatched family donors : impact of chronic GVHD.2009

    • Author(s)
      Kanda J, ら
    • Journal Title

      Bone Marrow Transplant 44

      Pages: 327-329

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oncogenic fusion E2A-HLF sensitize t(17 ; 19)-positive acute lymphoblastic leukemia to TRAIL-mediated apoptosis by upregulating the expression of death receptors

    • Author(s)
      Zhang X, Inukai T, Hirose K, Akahane K, Kuroda I, et al
    • Journal Title

      Leukemia

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] BCR-ABL regulates death receptor expression for TNF-related apoptosis-inducing ligand(TRAIL) in Philadelphia chromosome-positive leukemia

    • Author(s)
      Kuroda I, Inukai T, Akahane K, Hirose K, et al
    • Journal Title

      Oncogene

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] BCR-ABL regulates death receptor expression for TNF-related apoptosis-inducing ligand(TRAIL) inPhiladelphia chromosome-positive leukemia2011

    • Author(s)
      Kuroda I, Inukai T, Akahane K, HiroseK, et al
    • Organizer
      53th American Society of Hematology Annual Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      2011-12-11
    • Related Report
      2011 Final Research Report
  • [Presentation] BCR-ABL Regulates Death Receptor Expression for TNF-Related Apoptosis-Inducing Ligand (TRAIL) in Philadelphia Chromosome-Positive Leukemia2011

    • Author(s)
      Kuroda I, Inukai T, et al
    • Organizer
      アメリカ血液学会
    • Place of Presentation
      サンディェゴ国際会議場(アメリカ合衆国)
    • Year and Date
      2011-12-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Philadelphia染色体陽性白血病細胞におけるImatinibによる小胞体ストレス誘導作用とTRAIL感受性の検討2009

    • Author(s)
      張暁春,犬飼岳史,黒田格,赤羽弘資,廣瀬衣子, ほか
    • Organizer
      第51回日本小児血液学会総会
    • Place of Presentation
      幕張
    • Year and Date
      2009-11-28
    • Related Report
      2011 Final Research Report
  • [Presentation] T細胞型急性リンパ性白血病のTRAIL耐性へのTRAIL受容体DR4/DR5遺伝子のメチル化とプロモーター活性の関与2009

    • Author(s)
      赤羽弘資,犬飼岳史,廣瀬衣子,黒田格, ほか
    • Organizer
      第71回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-23
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] BCR-ABLはPh1陽性白血病細胞のTRAILに対するdeath受容体の発現に関与する2009

    • Author(s)
      黒田格,犬飼岳史,張暁春,廣瀬衣子,赤羽弘資, ほか
    • Organizer
      第71回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-23
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Philadelphia染色体陽性白血病細胞におけるImatinibによる小胞体ストレス誘導作用とTRAIL感受性の検討2009

    • Author(s)
      張曉春, ら
    • Organizer
      第51回日本小児血液学会総会
    • Place of Presentation
      浦安
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/pediatr/fpe/fpe110804.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/pediatr/fpe/fpe101110a.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/pediatr/fpe/fpe110804.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/pediatr/fpe/fpe110727.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/pediatr/fpe/fpe101110a.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/pediatr/fpe/fpe101110h.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/pediatr/fpe/fpe100819.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/pediatr/fpe/fpe100715.html

    • Related Report
      2010 Annual Research Report

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

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