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Molecular mechanisms of blast crisis transition and maintenance of leukemic stem cells in chronic myelogenous leukemia

Research Project

Project/Area Number 22890043
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

NAKAHARA Fumio  The University of Tokyo, 医科学研究所, 助教 (80581181)

Project Period (FY) 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
Fiscal Year 2010: ¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
Keywords白血病 / 白血病幹細胞 / 慢性骨髄性白血病 / 急性転化
Research Abstract

We show here that Hairy enhancer of split 1 (Hes1) has a role in blast crisis transition of CML. Hes1 is a basic helix-loop-helix transcriptional repressor that affects differentiation and often helps maintain cells in an immature state in various tissues. Also we show that expression of Hes1 immortalizes common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs). Whereas these cells did not develop myeloproliferative neoplasms when intravenously administered into irradiated mice, combination of Hes1 and BCR-ABL in both CMPs and GMPs caused a blast crisis of human CML-like disease, resulting in the rapid death of all the recipient mice. Intriguingly, Hes1 was highly expressed in 8 of 20 patients with CML in blast crisis, but not in the chronic phase, and dominant negative Hes1 retarded the growth of some CML cell lines expressing Hes1. These results taken together suggest that our model provides a good model to study mechanisms of the blast crisis transition in CML.

Report

(2 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (14 results)

All 2011 2010 Other

All Journal Article (9 results) (of which Peer Reviewed: 4 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] Two types of C/EBPalpha mutations play distinct but collaborative roles in leukemogenesis : lessons from clinical data and BMT models.2011

    • Author(s)
      Kato N., J.Kitaura, N.Doki, Y.Komeno, N.Watanabe-Okochi, K.Togami, F.Nakahara, T.Oki, Y.Enomoto, Y.Fukuchi, H.Nakajima, Y.Harada, H.Harada, T.Kitamura
    • Journal Title

      Blood 117

      Pages: 221-233

    • Related Report
      2010 Final Research Report
  • [Journal Article] 慢性骨髄性白血病の急性転化におけるHeslの関与2011

    • Author(s)
      中原史雄
    • Journal Title

      臨床血液

      Volume: in press掲載確定

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Two types of C/EBPα mutations play distinct but collaborative roles in leukemogenesis : lessons from clinical data and BMT models.2011

    • Author(s)
      Kato N
    • Journal Title

      Blood

      Volume: 117(1) Pages: 221-233

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] One-year low-dose valacyclovir as prophylaxis for varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation. A prospective study of the Japan Hematology and Oncology Clinical Study Group.2010

    • Author(s)
      Oshima K., T.Takahashi, T.Mori, T.Matsuyama, K.Usuki, Y.Asano-Mori, F.Nakahara, S.Okamoto, M.Kurokawa, Y.Kanda
    • Journal Title

      Transpl Infect Dis 12

      Pages: 421-427

    • Related Report
      2010 Final Research Report
  • [Journal Article] AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model.2010

    • Author(s)
      Komeno Y., J.Kitaura, N.Watanabe-Okochi, N.Kato, T.Oki, F.Nakahara, Y.Harada, H.Harada, R.Shinkura, H.Nagaoka, Y.Hayashi, T.Honjo, T.Kitamura
    • Journal Title

      Leukemia 24

      Pages: 1018-1024

    • Related Report
      2010 Final Research Report
  • [Journal Article] Hes1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogenous leukemia.2010

    • Author(s)
      Nakahara F., M.Sakata-Yanagimoto, Y.Komeno, N.Kato, T.Uchida, K.Haraguchi, K.Kumano, Y.Harada, H.Harada, J.Kitaura, S.Ogawa, M.Kurokawa, T.Kitamura, S.Chiba
    • Journal Title

      Blood 115

      Pages: 2872-2881

    • NAID

      10029425017

    • Related Report
      2010 Final Research Report
  • [Journal Article] One-year low-dose valacyclovir as prophylaxis for varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation. A prospective study of the Japan Hematology and Oncology Clinical Study Group.2010

    • Author(s)
      Oshima K
    • Journal Title

      Transplant Infectious Disease

      Volume: 12(5) Pages: 421-427

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model.2010

    • Author(s)
      Komeno Y
    • Journal Title

      Leukemia

      Volume: 24(5) Pages: 1018-1024

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hesl immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogenous leukemia.2010

    • Author(s)
      Nakahara F
    • Journal Title

      Blood

      Volume: 115(14) Pages: 2872-2881

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Hes1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myeloid leukemia.2011

    • Author(s)
      Fumio Nakahara, Toshio Kitamura, 他
    • Organizer
      日米血液腫瘍セミナー2011
    • Place of Presentation
      神奈川県葉山湘南国際村センター
    • Year and Date
      2011-02-26
    • Related Report
      2010 Final Research Report
  • [Presentation] Hesl immortalizes committed progenitors and plays a role in blast crisis transition in chronic myeloid leukemia.2011

    • Author(s)
      中原史雄
    • Organizer
      日米血液腫瘍セミナー2011
    • Place of Presentation
      葉山湘南国際村センター
    • Year and Date
      2011-02-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] Hes1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myeloid leukemia.2011

    • Author(s)
      Fumio Nakahara, Toshio Kitamura, 他
    • Organizer
      「個体レベルでのがん研究支援活動」ワークショップ
    • Place of Presentation
      滋賀県琵琶湖ホテル
    • Year and Date
      2011-02-03
    • Related Report
      2010 Final Research Report
  • [Presentation] Hairy enhance of split1 (Hes1)による造血前駆細胞の不死化と慢性骨髄性白血病の急性転化誘導2011

    • Author(s)
      中原史雄
    • Organizer
      「個体レベルでのがん研究支援活動」ワークショップ
    • Place of Presentation
      滋賀県琵琶湖ホテル
    • Year and Date
      2011-02-03
    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2010-08-27   Modified: 2016-04-21  

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