Molecular mechanisms maintaining leukemic stem cells by forkhead transcription factor Foxo

• Project/Area Number: 20590394
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kanazawa University
• Principal Investigator: NAKA Kazuhito Kanazawa University, がん研究所, 准教授 (70372688)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: がん幹細胞 / 慢性骨髄性白血病 / 抗がん剤抵抗性 / FOXO / TGF-・阻害剤 / チロシンキナーゼ阻害剤抵抗性 / TGF-β阻害剤 / 白血病幹細胞 / フォークヘッド転写因子 / がん / 白血病

Research Abstract

In this study, we demonstrated a critical role for the TGF-β-FOXO pathway in maintenance and imatinib resistance of leukemia-initiating cells (LICs) in chronic myeloid leukemia (CML) which are responsible for recurrence of disease. TGF-β inhibitor in combination with imatinib treatment led to efficient depletion of LICs in vivo.

Research Products

• [Journal Article] Suppression of glioma-initiating cell self-renewal by NKX2.2. (2011)
  • Author(s): Muraguchi T., Tanaka S., Yamada D., Tamase A., Nakada M., Nakamura H., Hoshii T., Ooshio T., Tadokoro Y., Naka K., Ino Y., Todo T., Kuratsu J., Saya H., Hamada J., Hirao A.
  • Journal Title: Cancer Res. 71(3) Pages: 1135-1145
  • Peer Reviewed
• [Journal Article] TGF-β-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. (2010)
  • Author(s): Naka K., Hoshii T., Muraguchi T., Tadokoro Y., Ooshio T., Kondo Y., Nakao S., Motoyama N., Hirao A.
  • Journal Title: Nature 463(7281) Pages: 676-680
  • NAID: 40018725961
  • Peer Reviewed
• [Journal Article] A novel therapeutic approach to eradicate tyrosine kinase inhibitor resistant chronic myeloid leukemia stem cells. (2010)
  • Author(s): Naka K., Hoshii T., Hirao A.
  • Journal Title: Cancer Science. 101(7) Pages: 1577-1581
  • NAID: 10026594276
  • Peer Reviewed
• [Journal Article] A novel therapeutic approach to eradicate tyrosine kinase inhibitor resistant chronic mveloid leukemia stem cells (2010)
  • Author(s): Naka K., Hoshii T., Hirao A
  • Journal Title: Cancer Science Volume: 101 Pages: 1577-1581
  • Peer Reviewed
• [Journal Article] TGF-β-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. (2010)
  • Author(s): Naka K., Hoshii T., Hirao A., 他
  • Journal Title: Nature 463 Pages: 676-680
  • NAID: 40018725961
  • Peer Reviewed
• [Journal Article] Identification of tumor-initiating cells responsible for invasiveness in a genetically homogeneous, highly aggressive brain tumor. (2009)
  • Author(s): Tamase A., Muraguchi T., Naka K., Hirao A., 他
  • Journal Title: Proc.Natl.Acad.Sci.U.S.A. 106 Pages: 17163-17168
  • Peer Reviewed
• [Journal Article] Identification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity. (2008)
  • Author(s): 大村昌子, 仲一仁, 平尾敦, 他
  • Journal Title: Stem Cells 26 Pages: 3237-3246
  • Peer Reviewed
• [Presentation] Molecular Mechanism Regulating Foxo In Leukemia Initiating Cells of Chronic Myeloid Leukemia. (2010)
  • Author(s): 仲一仁, 他7名, 1番目
  • Organizer: アメリカ血液学会
  • Place of Presentation: Orange County Convention Center(アメリカ,オーランド)
  • Year and Date: 2010-12-06
• [Presentation] TGF-β-FOXOシグナルによる白血病幹細胞の治療抵抗性機構 (2010)
  • Author(s): 仲一仁
  • Organizer: 第16回血液科学セミナー
  • Place of Presentation: 京王プラザホテル(東京都新宿区)(招待講演)
  • Year and Date: 2010-10-24
• [Presentation] Molecular mechanism regulating FOXO in leukemia initiating cells of chronic myeloid leukemia. (2010)
  • Author(s): 仲一仁, 他8名, 1番目
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2010-09-25
• [Presentation] Analyses of molecular mechanism regulating FOXO in leukemia initiating cells of chronic myeloid leukemia. (2010)
  • Author(s): 仲一仁, 他6名, 1番目
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府大阪市)
  • Year and Date: 2010-09-24
• [Presentation] TGF-β-FOXOシグナルによる白血病幹細胞の抗がん剤抵抗性機構の解析 (2010)
  • Author(s): 仲一仁, 平尾敦
  • Organizer: 第19回日本がん転移学会
  • Place of Presentation: 金沢市文化ホール(石川県金沢市)(招待講演)
  • Year and Date: 2010-06-16
• [Presentation] Foxo3a is essential for survival of leukemia-initiating cells in chronic myeloid leukemia (2010)
  • Author(s): 仲一仁, 他7名, 1番目
  • Organizer: アメリカがん学会
  • Place of Presentation: Walter E. Washington Convention Center (アメリカ, ワシントンDC)
  • Year and Date: 2010-04-20
• [Presentation] Molecular Mechanism Regulating Foxo In Leukemia Initiating Cells of Chronic Myeloid Leukemia. (2010)
  • Author(s): Kazuhito Naka, Takayuki Hoshii, Yuko Tadokoro, Takako Ooshio, Yukio Kondo, Shinji Nakao, Noboru Motoyama, Atsushi Hirao
  • Organizer: The 52^<nd> American Society of Hematology Annual meeting and exposition
  • Place of Presentation: Orange County Convention Center (USA)
• [Presentation] TGF-β-FOXOシグナルによる白血病幹細胞の治療抵抗性機構 (2010)
  • Author(s): 仲一仁
  • Organizer: 第16回血液科学セミナー
  • Place of Presentation: 京王プラザホテル(東京都)
• [Presentation] Molecular mechanism regulating FOXO in leukemia initiating cells of chronic myeloid leukemia. (2010)
  • Author(s): Kazuhito Naka, Takayuki Hoshii, Teruyuki Muraguchi, Yoko Tadokoro, Takako Ooshio, Yukio Kondo, Shinji Nakao, Noboru Motoyama, Atsushi Hirao
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜国立横浜国際会議場(神奈川県)
• [Presentation] Analyses of molecular mechanism regulating FOXO in leukemia initiating cells of chronic myeloid leukemia. (2010)
  • Author(s): Kazuhito Naka, Takayuki Hoshii, Teruyuki Muraguchi, Yoko Tadokoro, Takako Ooshio, Noboru Motoyama, Atsushi Hirao
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
• [Presentation] 白血病幹細胞の抗がん剤抵抗性機構の解析 (2010)
  • Author(s): 仲一仁, 平尾敦
  • Organizer: 第19回日本癌病態治療研究会
  • Place of Presentation: 東京ステーションコンファレンス(東京都)
• [Presentation] TGF-β-FOXOシグナルによる白血病幹細胞の抗がん剤抵抗性機構の解析 (2010)
  • Author(s): 仲一仁, 平尾敦
  • Organizer: 第19回日本がん転移学会
  • Place of Presentation: 金沢市文化ホール(石川県)
• [Presentation] Foxo3a is essential for survival of leukemia-initiating cells in chronic myeloid leukemia. (2010)
  • Author(s): Kazuhito Naka, Takayuki Hoshii, Teruyuki Muraguchi, Yuko Tadokoro, Takako Ooshio, Noboru Motoyama, Masanobu Oshima, Atsushi Hirao
  • Organizer: American Association for Cancer Research 101st Annual meeting
  • Place of Presentation: Walter E.Washington Convention Center (USA)
• [Presentation] Foxo3a is essential for maintenance of chronic myelogenous leukemia-initiating cells. (2009)
  • Author(s): Kazuhito Naka, Takayuki Hoshii, Teruyuki Muraguchi, Yoko Tadokoro, Takako Ooshio, Noboru Motoyama, Atsushi Hirao
  • 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(京都府)
• [Presentation] Foxo3a is essential for maintenance of chronic myelogenous leukemia-initiating cells. (2009)
  • Author(s): Kazuhito Naka, Takayuki Hoshii, Teruyuki Muraguchi, Yoko Tadokoro, Takako Ooshio, Noboru Motoyama, Atsushi Hirao
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜国立横浜国際会議場(神奈川県)
• [Presentation] Foxo3a is essential for survival of chronic myeloid leukemia-initiating cells. (2009)
  • Author(s): Kazuhito Naka, Takayuki Hoshii, Teruyuki Muraguchi, Takako Ooshio, Noboru Motoyama, Atsushi Hirao
  • Organizer: 7^<th> International Society of Stem Cell Research
  • Place of Presentation: Centre Convencions Internacional Barcelona (Spain)
• [Presentation] Foxo3a is essential for maintenance of chronic myelogenous leukemia-initiating cells. (2009)
  • Author(s): Kazuhito Naka, Takayuki Hoshii, Teruyuki Muraguchi, Yoko Tadokoro, Takako Ooshio, Noboru Motoyama, Atsushi Hirao
  • Organizer: 第7回幹細胞シンポジウム
  • Place of Presentation: 泉ガーデンギャラリー(東京都)
• [Presentation] Foxo3a is essential for maintenance of chronic myelogenous leukemia-initiating cells. (2009)
  • Author(s): 仲一仁・平尾敦, 他
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] Foxo3a is essential for maintenance of chronic myelogenous leukemia-initiating cells. (2009)
  • Author(s): 仲一仁・平尾敦, 他
  • Organizer: 第68回日本癌学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] Nucleostemin-GFPレポーターシステムによる白血病幹細胞の同定 (2008)
  • Author(s): 仲一仁, 平尾敦, 他
  • Organizer: 第67回日本癌学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-28
• [Presentation] Nucleostemin-GFPレポークシステムによる白血病幹細胞の同定 (2008)
  • Author(s): 仲一仁, 平尾敦, 他
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2008-10-11
• [Book] がんの"幹細胞らしさ"と治療抵抗性のメカニズム 29(2) (2011)
  • Author(s): 仲一仁, 平尾敦
  • Publisher: 実験医学
• [Book] Annual Review血液 2010 (2011)
  • Author(s): 仲一仁, 平尾敦
  • Publisher: 中外医学社
• [Book] がん幹細胞マーカーと分子標的,癌の分子標的治療 (2008)
  • Author(s): 仲一仁, 平尾敦
  • Publisher: 南山堂
• [Remarks] ホームページ等
  • URL: http://www.kanazawa-u.ac.jp/~ganken/hirao-hp/index.html
• [Remarks]
  • URL: http://kurt.kanazawa-u.ac.jp/souran_ku/info.php?teacher_id=185
• [Remarks]
  • URL: http://kurt.kanazawa-u.ac.jp/souran_ku/info.php?teacher_id=185
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/~ganken/hirao-hp/index.html
• [Patent(Industrial Property Rights)] 白血病治療剤及び該治療剤の新規なスクリーニング (2009)
  • Inventor(s): 平尾敦, 仲一仁
  • Industrial Property Rights Holder: 平尾敦, 仲一仁, 金沢大学
  • Industrial Property Number: 2009-134714
  • Acquisition Date: 2009-06-04
• [Patent(Industrial Property Rights)] 白血病治療剤及び該治療剤の新規なスクリーニング (2009)
  • Inventor(s): 平尾敦, 仲一仁
  • Industrial Property Rights Holder: 金沢大学
  • Industrial Property Number: 2009-134714
  • Filing Date: 2009-06-04