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Molecular basis of central neurvous invasion of pediatric leukemia

Research Project

Project/Area Number 25461593
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionShimane University

Principal Investigator

FUKDUA SEIJI  島根大学, 医学部, 教授 (30273147)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords急性骨髄性白血病 / 細胞遊走 / 浸潤 / FLT/ITD / CXCL12 / CXCR4 / 急性白血病 / ケモカイン / 髄外浸潤 / 中枢神経浸潤 / 白血病細胞浸潤 / 白血病細胞遊走異常
Outline of Final Research Achievements

One of the major indicators of poor prognosis in leukemia patients is extramedullary infiltration or dissemination of leukemia cells. In particular, leukemia cell infiltration into the central nervous system is one of the major complications negatively influencing prognosis. However, little is known about the mechanisms responsible for extramedullary dissemination of leukemia cells compared to those responsible for solid tumor metastasis. In the present study, we have identified molecular mechanism responsible for the enhanced chemotaxis towards chemokine CXCL12 that is induced by the Internal Tandem Duplication mutation of FLT3 gene (FLT3/ITD) associated with extremely poor prognosis. We subsequently investigated if antagonizing this particular molecular mechanism can be utilized for the treatment to block the unnecessary migration of the hematopoietic cells with FLT3/ITD.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (13 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (7 results) (of which Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] Indiana University School of Medicine(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Indiana University School of Medicine(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Internal Tandem Duplication in FLT3 Attenuates Proliferation and Regulates Resistance to the FLT3 Inhibitor AC220 by Modulating p21Cdkn1a and Pbx1 in Hematopoietic Cells2016

    • Author(s)
      Abe M, Pelus LM, Singh P, Hirade T, Onishi C, Purevsuren J, Taketani T, Yamaguchi S, Fukuda S
    • Journal Title

      PLOS One

      Volume: 11 Issue: 7 Pages: 1-26

    • DOI

      10.1371/journal.pone.0158290

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Internal tandem duplication of FLT3 deregulates proliferation2016

    • Author(s)
      Tomohiro Hirade, Mariko Abe Chie Onishi, Takeshi Taketani, Seiji Yamaguchi, Seiji Fukuda
    • Journal Title

      International Journal of Hematology

      Volume: 103 Issue: 1 Pages: 95-106

    • DOI

      10.1007/s12185-015-1908-8

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Internal Tandem Duplication of Mutations in Flt3 Augment Chemotaxis by Blocking the Down-regulation of Rho-Associated Kinase via CXCL12/CXCR4 signaling axis.2014

    • Author(s)
      Onishi C, Mori-Kimachi S, Hirade T, Abe M, Taketani T, Suzumiya J, Sugimoto T, Yamaguchi S, Kapur R, Fukuda S
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 45 Pages: 31053-31065

    • DOI

      10.1074/jbc.m114.568287

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Flt3/ITD陽性白血病の治療抵抗機構2016

    • Author(s)
      福田誠司
    • Organizer
      島根大学病態生化学セミナー
    • Place of Presentation
      出雲市
    • Year and Date
      2016-11-28
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Flt3/ITD confers resistance to Flt3/ITD inhibitor AC220 by up-regulating Runx12015

    • Author(s)
      Seiji Fukuda, Tomohiro Hirade, Mariko Abe Chie Onishi, Takeshi Taketani, Seiji Yamaguchi
    • Organizer
      77th annual meeting of Japanese Society of Hematology
    • Place of Presentation
      金沢 (石川県立音楽堂)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
  • [Presentation] Flt3/ITD Enhances Hematopoietic Cell Migration towards Chemokine CCL2 Independent of Blocking the Negative Feedback Mechanism on Rho-Associated Kinase2014

    • Author(s)
      Seiji Fukuda, Chie Onishi*, Tomohiro Hirade, Mariko Abe, Takeshi Taketani, Seiji Yamaguchi
    • Organizer
      56th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      San Fransisco, USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Flt3/ITD mutation enhances hematopoietic cell migration towards chemokine CCL2: MCP12014

    • Author(s)
      Seiji Fukuda, Tomohiro Hirade, Mariko Abe, Takeshi Taketani, Seiji Yamaguchi
    • Organizer
      第56回小児血液がん学会
    • Place of Presentation
      (岡山) 岡山コンベンションセンター
    • Year and Date
      2014-11-28 – 2014-11-30
    • Related Report
      2014 Research-status Report
  • [Presentation] ITD-Flt3はSDF1によるRock1の発現減少を阻害することで細胞遊走を亢進する2013

    • Author(s)
      平出智裕、福田誠司、大西千恵、安部真理子、山口清次
    • Organizer
      第116回日本小児科学会学術集会
    • Place of Presentation
      広島、広島国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] ITD-Flt3 accentuates cell migration by antagonizing the reduction of ROCK1 induced by SDF12013

    • Author(s)
      Chie Onishi, Tomohiro Hirade, Seiji Yamaguchi and Seiji Fukuda
    • Organizer
      第75回日本血液学会総会
    • Place of Presentation
      札幌、ロイトン札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] Flt3-ligand enhances chemotaxis to SDF1 by blocking the down-regulation of Rock1 that is induced by SDF12013

    • Author(s)
      Seiji Fukuda, Tomohiro Hirade, Seiji Yamaguchi and Chie Onishi
    • Organizer
      第75回日本血液学会総会
    • Place of Presentation
      札幌、ロイトン札幌
    • Related Report
      2013 Research-status Report
  • [Remarks] 島根大学小児科

    • URL

      http://www.med.shimane-u.ac.jp/pediatrics/2-3/2-3.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2022-02-16  

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