Analysis of leukemogenesis through the NPM fusion gene

• Project/Area Number: 24790971
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kyoto 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: ¥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.

Research Products

• [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
  • Peer Reviewed / Open Access
• [Journal Article] Absent or Extremely Low Neutrophil Alkaline Phosphatase Activity Levels in Patients with Myelodysplastic Syndromes (2013)
  • 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
  • Peer Reviewed
• [Journal Article] H2.0-like homeobox (HLX) regulates early hematopoiesis and promotes acute myeloid leukemia (2012)
  • 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
  • Peer Reviewed
• [Presentation] A Rare Population of Stem Cell Memory T Cells Is an Apex of the Hierarchy of Adult T-Cell Leukemia (2013)
  • 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
• [Presentation] KDM1A is involved in the myelomonocytic/erythroid differentiation and is a promising target of AML (2013)
  • 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
• [Presentation] Challenge to identify ATL-initiating cells (2013)
  • 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
• [Presentation] Retrospective analysis of allogeneic HSCT for MDS : A single institution experience (2013)
  • 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
• [Presentation] Search for pathogenesis of acquired myelodysplastic syndromes using reprogramming technology (2013)
  • 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
• [Presentation] A case of blastic plasmacytoid dendritic cell neoplasm with MLL-ENL fusion (2013)
  • 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
• [Presentation] Successful allo-SCT following mogamulizumab for a patient with refractory ATL (2013)
  • 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
• [Presentation] Clonal and hierarchical expansion of adult T-cell leukemia cells in stem cell memory T-cell subset (2013)
  • 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
• [Presentation] Inhibition of KDM1A suppresses the growth of acute myeloid leukemia or myelodysplastic syndromes cells through inducing differentiation (2013)
  • 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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Retrospective analysis of allogeneic SCT for therapy-related MDS/AML : A single center experience (2012)
  • 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
• [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
• [Book] BIO Clinica (2012)
  • Author(s): 河原 真大
  • Total Pages: 5
  • Publisher: 北隆館
• [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
• [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
• [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
  • 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
  • Overseas