Roles ofAML1 mutants in the development of myelodysplastic syndromes

• Project/Area Number: 20599009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: SATOH Yusuke Osaka University, 医学系研究科, 助教 (20506307)
• Co-Investigator(Kenkyū-buntansha): KANAKURA Yuzuru 大阪大学, 医学系研究科, 助教 (20177489) ; YOKOTA Takafumi 大阪大学, 医学系研究科, 助教 (60403200) ; MAEDA Tetsuo 大阪大学, 医学系研究科, 助教 (00403064) ; MATSUMURA Itaru 大阪大学, 医学系研究科, 准教授 (00294083)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,970,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥570,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 骨髄異形成症候群 / 急性骨髄性白血病 / AML1 / RUNX1 / DNA修復 / MDS / STAT5

Research Abstract

We performed the functional analysis of AML1dC, which is a dominant negative mutant of AML1. As a result, we found that AML1dC enhances proliferating ability of hematopoietic stem/progenitor cells (HSPC ) and attenuates DNA repair ability of HSPC. Through these mechanisms, AML1dC promotes the development of myelodysplastic syndromes (MDS) and the transition from MDS to acute myeloid leukemia.

Research Products

• [Journal Article] Myeloid neoplasm-related gene abnormalities differentially affect dendritic cell differentiation from marine hematopoietic stem/progenitor cells. (2011)
  • Author(s): Fujita J, Mizuki M, Otsuka M, Ezoe S, Tanaka H, Satoh Y, Fukushima K, Tokunaga M, Matsumura I, Kanakura Y.
  • Journal Title: Immunol.Lett. 136 Pages: 61-73
  • Peer Reviewed
• [Journal Article] Myeloid neoplasm-related gene abnormalities differentially affect dendritic cell differentiation from murine hematopoietic stem/progenitor cells. (2011)
  • Author(s): Fujita J, Satoh Y, et al.
  • Journal Title: Immunol.Lett. Volume: (In press)
  • Peer Reviewed
• [Journal Article] BCR-ABL but not JAK2 V617F inhibits erythropoiesis through the Ras signal by inducing p21CIP1/WAF1. (2010)
  • Author(s): Tokunaga M, Ezoe S, Tanaka H, Satoh Y, Fukushima K, Matsui K, Shibata M, Tanimura A, Oritani K, Matsumura I, Kanakura Y.
  • Journal Title: J.Biol.Chem. 285 Pages: 31774-31782
  • Peer Reviewed
• [Journal Article] BCR-ABL but not JAK2 V617F inhibits erythropoiesis through the Ras signal by inducing p21CIP1/WAF1. (2010)
  • Author(s): Tokunaga M, Satoh Y, et al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 31774-31782
  • Peer Reviewed
• [Journal Article] Antifungal activity of micafungin in serum. (2009)
  • Author(s): Ishikawa J, Maeda T, Matsurnura I, Ujiie H, Masaie H, Nakazawa T, Mochizuki N, Kishino S, Kanakura Y.
  • Journal Title: Antimicrob.Agents Chemother. 53 Pages: 4559-4562
  • Peer Reviewed
• [Journal Article] The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice. (2009)
  • Author(s): Yokota T Oritani K, Butz S, Kokame K, Kincade P, Miyata T, Vestweber D, Kanakura Y.
  • Journal Title: Blood. 113 Pages: 2914-2923
  • Peer Reviewed
• [Journal Article] FIP1L1-PDGFRalpha imposes eosinophil lineage commitment on hematopoietic stem/progenitor cells. (2009)
  • Author(s): Fukushima K, Matsumura I, Ezoe S, Tokunaga M, Yasumi M, Satoh Y, Shibayama H, Tanaka H, Iwama A, Kanakura Y.
  • Journal Title: J.Biol.Chem. 284 Pages: 7719-7732
  • Peer Reviewed
• [Journal Article] FIP1L1-PDGFRalpha imposes eosinophil lineage commitment on hematopoietic stem/progenitor cells (2009)
  • Author(s): Fukushima K, Matsumura I, et. al.
  • Journal Title: J.Biol.Chem. 284 Pages: 7719-7732
  • Peer Reviewed
• [Journal Article] Antifungal activity of micafungin in serum (2009)
  • Author(s): Ishikawa T, Maeda T, et. al.
  • Journal Title: Antimicrob. Agents Chemother. 53 Pages: 4559-4562
  • Peer Reviewed
• [Journal Article] The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice (2009)
  • Author(s): Yokota T, et. al.
  • Journal Title: Blood 113 Pages: 2914-2923
  • Peer Reviewed
• [Journal Article] The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice (2009)
  • Author(s): Takafumi Yokota et.al.
  • Journal Title: Blood (in press)
  • Peer Reviewed
• [Journal Article] AML1/RUNX1 Works as a Negative Regulator of c-Mpl in Hematopoietic Stem Cells. (2008)
  • Author(s): Satoh Y, Matsumura I, Tanaka H, Ezoe S, Fukushima K, Tokunaga M, Yasumi M, Shibayama H, Mizuki M, Era T, Okuda T, Kanakura Y.
  • Journal Title: J.Biol.Chem. 283 Pages: 30045-30056
  • Peer Reviewed
• [Journal Article] Soluble frizzled-related protein 1 is estrogen inducible in bone marrow stromal cells and suppresses the earliest events in lymphopoiesis. (2008)
  • Author(s): Yokota T, Oritani K, Garrett KP, Kouro T, Nishida M, Takahashi I, Ichii M, Satoh Y, Kincade PW, Kanakura Y.
  • Journal Title: J.Immunol. 181 Pages: 6061-6072
  • Peer Reviewed
• [Journal Article] AML1/RUNX1 Works as a Negative Regulator of c-Mpl in Hematopoietic Stem Cells (2008)
  • Author(s): Yusuke Satoh et.al.
  • Journal Title: J. Biol. Chem 283 Pages: 30045-30056
  • Peer Reviewed
• [Journal Article] Soluble frizzled-related protein 1 is estrogen inducible in bone marrow stromal cells and suppresses the earliest events in lymphopoiesis (2008)
  • Author(s): Takafumi Yokota et.al.
  • Journal Title: J. Immunol 181 Pages: 6061-6072
  • Peer Reviewed
• [Journal Article] Predictability of the response to tyrosine kinase inhibitors via in vitro analysis of Ber-Abl phosphorylation.
  • Author(s): Shibata M, Ezoe S, Oritani K, Matsui K, Tokunaga M, Fujita N, Saito Y, Takahashi T, Hino M, Matsumura I, Kanakura Y.
  • Journal Title: Leak.Res. In press.
  • Peer Reviewed
• [Presentation] リンパ球の初期分化誘導分子の探索と機能解析 (2010)
  • Author(s): 佐藤友亮
  • Organizer: 第16回血液科学セミナー
  • Place of Presentation: 京王プラザホテル(東京)(招待講演)
  • Year and Date: 2010-10-23
• [Presentation] C-terminal mutation of RUNX1 deteriorates DNA damage-repair response and promotes the development of AML. (2010)
  • Author(s): 佐藤友亮
  • Organizer: The 17th international RUNX workshop.
  • Place of Presentation: オリエンタルホテル広島(広島)
  • Year and Date: 2010-07-14
• [Presentation] RUNX1変異とDNA損傷修復経路の異常 (2010)
  • Author(s): 佐藤友亮
  • Organizer: 第8回先端血液学セミナー
  • Place of Presentation: ホテルニューオータニ東京(東京)(招待講演)
  • Year and Date: 2010-05-29
• [Presentation] C-Terminal Mutation of RUNX1 Deteriorates DNA Damage-Repair Response and Promotes the Development of Acute Myeloid Leukemia. (2009)
  • Author(s): 佐藤友亮
  • Organizer: The American Society of Hematology 51st Annual meeting.
  • Place of Presentation: ニユーオリンズ
  • Year and Date: 2009-12-07
• [Presentation] RUNX1 controls nucleotide excision repair (NER) system through transcriptional regulation of Gadd45a (2009)
  • Author(s): 佐藤友亮
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2009-10-23
• [Presentation] RUNXIはGadd45aの転写調節を介してヌクレオチド除去修復を制御する (2009)
  • Author(s): 佐藤友亮
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2009-10-02
• [Presentation] C-Terminal Mutation of RUNX1 Deteriorates DNA Damage-Repair Response and Promotes the Development of Acute Myeloid Leukemia (2009)
  • Author(s): Yusuke Satoh
  • Organizer: The American Society of Hematology 51st Annual meeting
  • Place of Presentation: New Orleans, USA
• [Presentation] Roles for the AML1/RUNX1 Point Mutation in the Pathogenesis of MDS/AML. (2008)
  • Author(s): 佐藤友亮
  • Organizer: The American Society of Hematology 50th Annual meeting.
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2008-12-06
• [Presentation] Roles for the AML1/RUNX1 Point Mutation in the Pathogenesis of MDS/AML (2008)
  • Author(s): Yusuke Satoh
  • Organizer: The American Society of Hematology 50th Annual meeting
  • Place of Presentation: サンフランシスコ