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Analysis of leukemogenesis through the NPM fusion gene

Research Project

Project/Area Number 24790971
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKyoto University

Principal Investigator

KAWAHARA Masahiro  京都大学, 医学(系)研究科(研究院), 助教 (80617449)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords白血病 / 造血幹細胞 / NPM1 / MLF1
Research Abstract

We analyzed a mechanism for leukemogenesis through the NPM-MLF1 fusion gene and overexpression of wild-type MLF1. We found that clonogenic capacity is transiently enhanced and Kit-positive immature hematopoietic cells are increased by transduction of NPM-MLF1 and MLF1 into murine hematopoietic stem and progenitor cells (HSPCs), and MLF1 expression level is high in hematopoietic stem cells but decreases as differentiation, indicating that NPM-MLF1 and overexpression of MLF1 might contribute to leukemogenesis through dysregulation of normal differentiation of HSPCs.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (24 results)

All 2014 2013 2012 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (15 results) Book (2 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] A case of minor BCR-ABL1 positive acute lymphoblastic leukemia following essential thrombocythemia and originating from a clone distinct from that harboring the JAK2-V617F mutation.2014

    • Author(s)
      Nagai Y, Kawahara M, Sugino N, Shimazu Y, Hishizawa M, Yamashita K, Kadowaki N, Takaori-Kondo A
    • Journal Title

      Experimental Hematology & Oncology

      Volume: 3 Issue: 1 Pages: 6-6

    • DOI

      10.1186/2162-3619-3-6

    • NAID

      120005411358

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Absent or Extremely Low Neutrophil Alkaline Phosphatase Activity Levels in Patients with Myelodysplastic Syndromes2013

    • Author(s)
      Yoshida Y, Katsurada T, Oguma S, Nakabo Y, Yoshinaga N, Kawahara M, Kawabata H.
    • Journal Title

      Internal Medicine

      Volume: 52 Issue: 4 Pages: 479-482

    • DOI

      10.2169/internalmedicine.52.9114

    • NAID

      130003365905

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] H2.0-like homeobox (HLX) regulates early hematopoiesis and promotes acute myeloid leukemia2012

    • Author(s)
      Kawahara M, Pandolfi A, Bartholdy B, Barreyro L, Will B, Roth M, Okoye UC, Todorova T, Figueroa ME, Melnick A, Mitsiades CS, Steidl U
    • Journal Title

      Cancer Cell

      Volume: 22 Issue: 2 Pages: 194-208

    • DOI

      10.1016/j.ccr.2012.06.027

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] A Rare Population of Stem Cell Memory T Cells Is an Apex of the Hierarchy of Adult T-Cell Leukemia2013

    • Author(s)
      Nagai Y, Kawahara M, Hishizawa M, Sugino N, Shimazu Y, Takaori-Kondo A
    • Organizer
      The 55th ASH Annual Meeting and Exposition
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] KDM1A is involved in the myelomonocytic/erythroid differentiation and is a promising target of AML2013

    • Author(s)
      Sugino N, Kawahara M, Suzuki T, Nagai Y, Shimazu Y, Hishizawa M, Takaori-Kondo A
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Challenge to identify ATL-initiating cells2013

    • Author(s)
      Nagai Y, Kawahara M, Hishizawa M, Sugino N, Shimazu Y, Takaori-Kondo A
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Retrospective analysis of allogeneic HSCT for MDS : A single institution experience2013

    • Author(s)
      Kawase Y, Kondo T, Maeda T, Kawahara M, Kitawaki T, Kitano T, Yamashita K, Kawabata H, Takaori-Kondo A
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Search for pathogenesis of acquired myelodysplastic syndromes using reprogramming technology2013

    • Author(s)
      Chonabayashi K, Kawahara M, Watanabe A, Okita K, Nishizawa M, Kadowaki N, Takaori-Kondo A, Yamanaka S, Yoshida Y
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] A case of blastic plasmacytoid dendritic cell neoplasm with MLL-ENL fusion2013

    • Author(s)
      Nakabo Y, Katsurada Y, Kawabata H, Kondo T, Kawahara M, Kitawaki T, Takaori-Kondo A, Yoshida Y
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Successful allo-SCT following mogamulizumab for a patient with refractory ATL2013

    • Author(s)
      Kawata T, Kawase Y, Hishizawa M, Kawahara M, Kondo T, Kitano T, Kadowaki N, Ohmori K, Takaori-Kondo A
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Clonal and hierarchical expansion of adult T-cell leukemia cells in stem cell memory T-cell subset2013

    • Author(s)
      Nagai Y, Kawahara M, Hishizawa M, Sugino N, Shimazu Y, Takaori-Kondo A
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Inhibition of KDM1A suppresses the growth of acute myeloid leukemia or myelodysplastic syndromes cells through inducing differentiation2013

    • Author(s)
      Sugino N, Kawahara M, Suzuki T, Nagai Y, Shimazu Y, Hishizawa M, Takaori-Kondo A
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Clonal and hierarchical expansion of adult T-cell leukemia cells in stem cell memory T-cell subset.2013

    • Author(s)
      Yuya Nagai , Masahiro Kawahara , Masakatsu Hishizawa , Noriko Sugino , Yayoi Shimazu , and Akifumi Takaori-Kondo.
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Inhibition of KDM1A suppresses the growth of acute myeloid leukemia or myelodysplastic syndromes cells through inducing differentiation.2013

    • Author(s)
      Noriko Sugino, Masahiro Kawahara, Takayoshi Suzuki, Yuya Nagai, Yayoi Shimazu, Masakatsu Hishizawa, and Akifumi Takaori-Kondo
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] KDM1A is involved in the myelomonocytic/erythroid differentiation and is a promising target of AML.2013

    • Author(s)
      Noriko Sugino, Masahiro Kawahara, Takayoshi Suzuki, Yuya Nagai, Yayoi Shimazu, Masakatsu Hishizawa, and Akifumi Takaori-Kondo.
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] Challenge to identify ATL-initiating cells.2013

    • Author(s)
      Yuya Nagai, Masahiro Kawahara, Masakatsu Hishizawa ,Noriko Sugino, Yayoi Shimazu, and Akifumi Takaori-Kondo.
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] A Rare Population of Stem Cell Memory T Cells Is an Apex of the Hierarchy of Adult T-Cell Leukemia.2013

    • Author(s)
      Yuya Nagai, Masahiro Kawahara, Masakatsu Hishizawa ,Noriko Sugino, Yayoi Shimazu, and Akifumi Takaori-Kondo.
    • Organizer
      The 55th ASH Annual Meeting and Exposition
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Retrospective analysis of allogeneic SCT for therapy-related MDS/AML : A single center experience2012

    • Author(s)
      Fujita H, Kondou T, Sakamoto S, Kawahara M, Yamashita K, Kawabata H, Kadowaki N, Takaori-Kondo A
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Book] BIO Clinica 多遺伝子疾患, 「急性骨髄性白血病における疾患遺伝子研究」の項2012

    • Author(s)
      河原真大
    • Publisher
      北隆館
    • Related Report
      2013 Final Research Report
  • [Book] BIO Clinica2012

    • Author(s)
      河原 真大
    • Total Pages
      5
    • Publisher
      北隆館
    • Related Report
      2012 Research-status Report
  • [Remarks] 京都大学医学部附属病院血液腫瘍内科ホームページ

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~hemonc/research/leukemia.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 京都大学大学院医学研究科 血液・腫瘍内科学 白血病・腫瘍幹細胞研究

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~hemonc/research/leukemia.html

    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] リシン構造を有するLSD1 選択的阻害薬2013

    • Inventor(s)
      河原真大, 他7名
    • Industrial Property Rights Holder
      国立大学法人京都大学, 他4機関
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-11-28
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] リシン構造を有するLSD1選択的阻害薬2013

    • Inventor(s)
      Kawahara M 他7名
    • Industrial Property Rights Holder
      国立大学法人京都大学 他4機関
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-11-28
    • Related Report
      2013 Annual Research Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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