Drug resistance mediated by hypoxic bone marrow leukemia environment in chronic myelogenous leukemia

• Project/Area Number: 19790674
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: KURODA Junya Kyoto Prefectural University of Medicine, 医学研究科, 助教 (70433258)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥510,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: 慢性骨髄性白血病 / 低酸素 / 骨髄ニッチ / Bcr-Abl / 解糖系 / Glyoxalase-I / チロシンキナーゼ阻害剤 / 分子標的治療 / Bcr-Ab1

Research Abstract

低酸素環境における慢性骨髄性白血病(CML)細胞の薬剤耐性メカニズムと解糖系依存、ならびに低酸素下での薬剤耐性克服における分子標的としての解糖系解毒酵素Glyoxalase-I阻害の重要性がin vitro、in vivoで明らかになった。

Research Products

• [Journal Article] The Bcr-Abl kinase inhibitor INNO-406 induces autophagy and different modes of cell death execution in Bcr-Abl-positive leukemias. (2008)
  • Author(s): Kamitsuji Y, Kuroda J, Kimura S, Toyokuni S, Watanabe K, Ashihara E, Tanaka H, Yui Y, Watanabe M, Matsubara H, Mizushima Y, Hiraumi Y, Kawata E, Yoshikawa T, Maekawa T, Nakahata T, Adachi S.
  • Journal Title: Cell Death Differ 15 Pages: 1712-1722
• [Journal Article] ABT-737 is a useful component of combinatory chemotherapies for chronic myelogenous leukaemias with diverse drug resistance mechanisms. (2008)
  • Author(s): Kuroda J, Kimura S,Andreeff M,Ashihara E, Kamitsuji Y, Yokota A, Kawata E, Takeuchi M, Tanaka R, Murotani Y, Matsumoto Y, Tanaka H, Strasser A, Taniwaki M, Maekawa T.
  • Journal Title: Br J Haematol 140 Pages: 181-190
• [Journal Article] JAK2V617F-positive essential thrombocythemia and multiple myeloma with IGH/CCND1 gene translocation co-exits, but originate from separate clones (2008)
  • Author(s): Kuroda J, et.al.
  • Journal Title: Acta Haematologica 120 Pages: 177-181
  • Peer Reviewed
• [Journal Article] Anti-myeloma effect of Homoharringtonine with concomitant targeting of the myeloma-promoting molecules, Mc1-1, XIAP and 13-catenin (2008)
  • Author(s): Kuroda J, et.al.
  • Journal Title: International Journal of Hematology 87 Pages: 507-515
  • Peer Reviewed
• [Journal Article] ABT-737 is a useful component of combinatory chemotherapies for chronic myelogenous leukaemias with diverse drug resistance mechanisms (2008)
  • Author(s): Kuroda J
  • Journal Title: British Journa lo fHaematology 140 Pages: 181-190
  • Peer Reviewed
• [Journal Article] Apoptosis-based dual molecular targeting by INNO-406, a second generation Bcr-Abl inhibitor, and ABT-737, an inhibitor of anti-apoptotic Bcl-2 proteins, against Bcr-Abl-positive leukemia. (2007)
  • Author(s): Kuroda J, Kimura S, Strasser A, Andreeff M, O'Reilly LA, Ashihara E, Kamitsuji Y, Yokota A, Kawata E, Takeuchi M, Tanaka R, Tabe Y, Taniwaki M, Maekawa T.
  • Journal Title: Cell Death Differ 14 Pages: 1667-1677
• [Journal Article] INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system and cyclosporine A augments its in vivo activity. (2007)
  • Author(s): Yokota A, Kimura S, Masuda S, Ashihara E, Kuroda J, Sato K, Kamitsuji Y, Kawata E, Deguchi Y, Urasaki Y, Terui Y, Ruthardt M, Ueda T, Hatake K, Inui KI, Maekawa T.
  • Journal Title: Blood 109 Pages: 306-314
• [Journal Article] Apoptosis-based dual molecular targeting by INNO-406,a second generation Bcr-Abl inhibitor,and ABT-737,an inhibitor of anti-apoptotic Bcl-2 proteins,against Bcr-Abl-positive leukemia (2007)
  • Author(s): Kuroda J
  • Journal Title: Cell Death and Differentiation 14 Pages: 1667-1677
  • Peer Reviewed
• [Presentation] 低酸素環境適応性CML細胞に対するGlyoxalase-1阻害時の効果 (2008)
  • Author(s): 武内美紀,黒田純也,上辻由里,木村晋也,芦原英司,程原佳子,藤山佳秀,川谷誠、長田裕之、安井英子,梅澤一夫,鶴尾隆、前川平
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
• [Presentation] Glyoxalase-I inhibition eliminates hypoxia-adapted CML cells resistant to imatinib, dasatinib, and INNO-406. (2008)
  • Author(s): Takeuchi M , Kimura S, Kuroda J, Ashihara E, Kawatani M, Osada H, Umezawa K, Yasui E, Imoto M, Tsuruo T, Hodohara K, Nakahata T, Fujiyama Y, Maekawa T
  • Organizer: The American Society of Hematology 50th Annual Meeting and Exposition
  • Place of Presentation: San Francisco, Calfornia,USA
• [Presentation] Homoharringtonineのアポトーシス抵抗性分子多重阻害による抗骨髄腫効果 (2008)
  • Author(s): 黒田純也, ら
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
• [Presentation] 低酸素環境適応による慢性骨髄性白血病の治療抵抗性獲得機序とその克服. (2007)
  • Author(s): 武内美紀,黒田純也,木村晋也,芦原英司,上辻由里,程原佳子,藤山佳秀,安井英子,梅澤一夫,前川平
  • Organizer: 第69回日本血液学会・第49回日本臨床血液学会・合同総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-13
• [Presentation] 白血病の分子標的治療とBcl-2ファミリー (2007)
  • Author(s): 黒田純也
  • Organizer: 第69回日本血液学会総会・第49回日本臨床血液学会総会合同開催
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-11
• [Presentation] 白血病の分子標的治療とBcl-2ファミリー (2007)
  • Author(s): 黒田 純也
  • Organizer: 第69回日本血液学会総会・第49回日本臨床血液学会総会合同開催
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Presentation] 新規Bcr-Abl阻害剤INNO-406とBcl-2阻害剤ABT-737の併用による慢性骨髄性白血病治療戦略. (2007)
  • Author(s): 黒田純也、木村晋也、芦原英司、前川平
  • Organizer: 第11回がん分子標的治療研究会総会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-06
• [Presentation] Glyoxalase-I Is a Potential Therapeutic Target for Chronic Myelogenous Leukemia Cells That Have Acquired Drug Resistancethrough Adaptation to Hypoxia. (2007)
  • Author(s): Takeuchi M, Kuroda J, Kimura S, Ashihara E, Umezawa K, Yasui E, Kawatani M, Osada H, Hodohara K, Fujiyama Y, Maekawa T
  • Organizer: The 49th Annual Meeting of American Society of Hematology
  • Place of Presentation: Atlanta, Georgia, USA