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Pathogenesis of APOBEC3B in childhood leukemia

Research Project

Project/Area Number 16K10027
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TAKETANI TAKESHI  島根大学, 学術研究院医学・看護学系, 教授 (30359880)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsAPOBEC3B / 小児白血病 / ウイルス感染
Outline of Final Research Achievements

We examined whether APOBEC3B as a viral defense mechanism contributes to carcinogenesis in childhood leukemia. The frequency of APOBEC3B gene expression in pediatric leukemia samples was low, but C→T mutations were found in 50% of cases, regardless of APOBEC3B gene expression. In addition, cord blood-derived CD34-positive cells into which the shRNA of the IKAROS gene and the PAX5 gene and the TEL-AML1 fusion gene were introduced, respectively, and part of the APOBEC3B gene simultaneously expressed showed cloned proliferation. The clone was found to have reduced differentiation ability, enhanced self-renewal ability and reduced apoptosis. These results suggest that the APOBEC3B gene may contribute to leukemic transformation of pediatric preleukemic clones.

Academic Significance and Societal Importance of the Research Achievements

成人の発がんの機序として、紫外線や放射線、抗がん剤、喫煙などの外因子が知られているが、小児がんにおいては、外因子に暴露される機会が成人に比べて極めて少ない。今回、ウイルス防御の1つであるAPOBEC3Bが小児白血病の発症に寄与している可能性を示したことから、感冒などのウイルス感染の予防が小児がん発症の予防になる可能性を示した。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2017 2016

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

  • [Journal Article] Single nucleotide polymorphisms of the DGKB and VCAM1 genes are associated with granulocyte colony stimulating factor-mediated peripheral blood stem cell mobilization.2017

    • Author(s)
      Mishima S, Matsuda C, Ishihara T, Nagase M, Taketani T, Nagai A.
    • Journal Title

      Transfus Apher Sci

      Volume: 56 Issue: 2 Pages: 154-159

    • DOI

      10.1016/j.transci.2016.10.011

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status 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
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant

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Published: 2016-04-21   Modified: 2021-02-19  

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