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A new mouse model of acute B lymphocytic leukemia (B-ALL)

Research Project

Project/Area Number 23790434
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KURATA Morito  東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (40451926)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords白血病 / 発がん / B細胞 / preB-ALL / BLNK / C/EBPβ
Research Abstract

Blnk (Bash/SLP-65) encodes an adaptor protein of the B-cell receptor signaling and functions as a tumor suppressor. Loss of function mutations of BLNK have been observed in human preB-ALL, however, only a subset of Blnk ko mice develop preB-ALL, suggesting that cooperative events with Blnk deficiency are required for complete leukemogenesis. Retroviral tagging was performed to identify the cooperative genes, and the Cebpb locus was the most frequent common integration site. Cebpb encodes two protein isoforms of LAP and LIP. Transgenic mice bearing LAP or LIP were generated, mated with Blnk ko mice, and transgenic expression of LAP significantly accelerated the ALL onset of Blnkko/ko mice. Moreover, significant decrease of mature B-cells and increase of IL-7Rα-positive fractions in the bone marrow of non-neoplastic Blnkko/ko/LAP tg mice was evident. Knockdown of C/EBP〓 in a human preB-ALL cell line lacking BLNK expression suppressed cellular growth. These results indicate that C/EBP〓 LAP promotes leukemogenesis in the absence of BLNK including human B-ALL.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (10 results)

All 2012 2011

All Presentation (10 results)

  • [Presentation] The role of C/Ebpb in Blnk deficient pre-B ALL and B-cell differentiation2012

    • Author(s)
      倉田盛人,北川昌伸,後飯塚僚,北村大介,中村卓郎
    • Organizer
      第71回日本癌会総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Final Research Report
  • [Presentation] preB細胞性リンパ性白血病(preB-ALL) 発症におけるBLNKとC/EBPβの協調作用2012

    • Author(s)
      倉田盛人,北川昌伸,後飯塚僚,北村大介,中村卓郎
    • Organizer
      第101回日本病理会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] The role of C/Ebpb and Blnk cooperation in the pre-B ALL2012

    • Author(s)
      Morito Kurata, Yohei Kanno, Tomoko Takahara, Yukari Yamazaki, Daisuke Kitamura, Takuro Nakamura
    • Organizer
      Ninth international workshop on molecular aspects of myeloid stem cell development and leukemia.
    • Place of Presentation
      Cincinnati, USA.
    • Related Report
      2012 Final Research Report
  • [Presentation] The role of C/Ebpb in Blnk deficient pre-B ALL and B-cell differentiation.2012

    • Author(s)
      倉田盛人
    • Organizer
      第71回日本癌会総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Presentation] The role of C/Ebpb and Blnk cooperation in the pre-B ALL.2012

    • Author(s)
      倉田盛人
    • Organizer
      Ninth international workshop on molecular aspects of myeloid stem cell development and leukemia.
    • Place of Presentation
      Cincinnati, USA.
    • Related Report
      2012 Annual Research Report
  • [Presentation] preB細胞性リンパ性白血病(preB-ALL)発症におけるBLNKとC/EBPβの協調作用2012

    • Author(s)
      倉田盛人
    • Organizer
      第101回日本病理会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] プレB細胞性リンパ性白血病発症におけるC/ebpβとBLNK/IL-7 シグナルの協調作用について2011

    • Author(s)
      倉田盛人,北川昌伸,後飯塚僚,北村大介,中村卓郎
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Final Research Report
  • [Presentation] B細胞性リンパ性白血病発症におけるBLNKとC/EBPβの協調作用について2011

    • Author(s)
      倉田盛人,北川昌伸,後飯塚僚,北村大介,中村卓郎
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report 2011 Research-status Report
  • [Presentation] プレB細胞性リンパ性白血病発症におけるC/ebpβとBLNK/IL-7シグナルの協調作用について.2011

    • Author(s)
      倉田盛人 北川昌伸 後飯塚僚 北村大介 中村卓郎
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] B-ALLの発症におけるBLNKとC/EBPbetaの協調作用2011

    • Author(s)
      倉田盛人 北川昌伸 後飯塚僚 北村大介 中村卓郎
    • Organizer
      第26回発癌病理研究会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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