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Development of new treatment strategy targeting mitotic kinases in hematological malignancies

Research Project

Project/Area Number 20591131
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKochi University

Principal Investigator

IKEZOE Takayuki  Kochi University, 教育研究部・医療学系, 講師 (80294833)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords分裂期キナーゼ / 造血器悪性腫瘍 / 急性白血病 / JAK2キナーゼ / apoptosis / 悪性リンパ腫
Research Abstract

Polo-like kinase1 (PLK1) belongs to the family of serine/threonine kinases and plays an important role in centrosome maturation, bipolar spindle formation, and cytokinesis during mitosis. We found in this study that PLK1 was aberrantly highly expressed in freshly isolated leukemia cells from individuals with acute myelogenous leukemia (AML, n=50) and acute lymphoblastic leukemia (ALL, n=15) compared to bone marrow mononuclear cells from healthy volunteers (n=13) (AML, p=0.016; ALL, p=0.008), as measured by real-time RT-PCR. Down-regulation of PLK1 by a small interfering RNA (siRNA) in NB4 AML cells inhibited their proliferation. GW843682X is a novel selective PLK1 inhibitor. The compound induced growth inhibition, caused accumulation of cells in the G2/M phase of the cell cycle and mediated apoptosis of human leukemia cells. Taken together, targeting PLK1 may be a promising treatment strategy for individuals with leukemia.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (37 results)

All 2010 2009 2008

All Journal Article (27 results) (of which Peer Reviewed: 26 results) Presentation (10 results)

  • [Journal Article] AZ960, a novel Jak2 inhibitor induces growth arrest and apoptosis in adult T-cell leukemia cells.2010

    • Author(s)
      Yang J, Ikezoe T, Nishioka C, Furihata M, Yokoyama A.
    • Journal Title

      Mol Cancer Ther. 12

      Pages: 3386-3395

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] cells to multi-targeted tyrosine kinase inhibitor induces activations of AKT, ERK and STAT5 signaling via epigenetic silencing of the PTEN gene.2010

    • Author(s)
      Nishioka C, Ikezoe T, Yang J, Yokoyama A.
    • Journal Title

      Leukemia. 24

      Pages: 1631-1640

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Kinase inhibitor-mediated apoptosis in acute myelogenous leukemia cells.2010

    • Author(s)
      Ikezoe T, Yang J, Nishioka C, Yokoyama A.
    • Journal Title

      Int J Hematol. 91

      Pages: 69-77

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] mTORC1 by RAD001 (everolimus) potentiates the effects of 1,25-dihydroxyvitamin D(3) to induce growth arrest and differentiation of AML cells in vitro and in vivo.2010

    • Author(s)
      Yang J, Ikezoe T, Nishioka C, Ni L, Koeffler HP, Yokoyama A.
    • Journal Title

      Exp Hematol. 38

      Pages: 666-676

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] treatment of imatinib-resistant hypereosinophilic syndrome with nilotinib.2010

    • Author(s)
      Ikezoe T, Togitani K, Tasaka T, Nishioka C, Yokoyama A.
    • Journal Title

      Leuk Res. 34

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] induces apoptosis of acute myelogenous leukemia cells via inhibition of eukaryotic initiation factor 4E-binding protein 1 and down-regulation of Mcl-1.2010

    • Author(s)
      Nishioka C, Ikezoe T, Yang J, yokoyama A.
    • Journal Title

      Apoptosis. 15

      Pages: 795-804

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] AZ960, a novel Jak2 inhibitor, induces growth arrest and apoptosis in adult T-cell leukemia cells.2010

    • Author(s)
      Yang J
    • Journal Title

      Mol Cancer Ther

      Volume: 12 Pages: 3386-3395

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term exposure of leukemia cells to multi-targeted tyrosine kinase inhibitor induces activations of AKT, ERK and STAT5 signaling via epigenetic silencing of the PTEN gene.2010

    • Author(s)
      Nishioka C
    • Journal Title

      Leukemia

      Volume: 24 Pages: 1631-1640

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of mTORC1 by RAD001 (everolimus) potentiates the effects of 1,25-dihydroxyvitamin D(3) to induce growth arrest and differentiation of AML cells in vitro and in vivo.2010

    • Author(s)
      Yang J
    • Journal Title

      Exp Hematol

      Volume: 38 Pages: 666-676

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p53 is critical for the Aurora B kinase inhibitor-mediated apoptosis in acute myelogenous leukemia cells2010

    • Author(s)
      Ikezoe T
    • Journal Title

      Int J Hematolo 91

      Pages: 69-77

    • NAID

      10026110647

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] in non-Hodgkin lymphoma.2009

    • Author(s)
      Ikezoe T, Takeuchi T, Yang J, Adachi Y, Nishioka C, Furihata M, Koeffler HP, Yokoyama A.
    • Journal Title

      Lab Invest. 89

      Pages: 1364-1373

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] inhibitor stimulates expression of IL-6 and activates JAK2/STAT5 signaling in acute myelogenous leukemia cells.2009

    • Author(s)
      Nishioka C, Ikezoe T, Yang J, Yokoyama A.
    • Journal Title

      Leukemia. 23

      Pages: 2304-2308

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] receptor tyrosine kinase inhibitor, induces monocytic differentiation of acute myelogenous leukemia cells that is enhanced by 1,25-dihydroxyvitamin D(3).2009

    • Author(s)
      Nishioka C, Ikezoe T, Yang J, Yokoyama A.
    • Journal Title

      Leukemia. 23

      Pages: 2171-2173

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] signaling enhances the ability of cytarabine to induce growth arrest and apoptosis of acute myelogenous leukemia cells.2009

    • Author(s)
      Nishioka C, Ikezoe T, Yang J, Yokoyama A.
    • Journal Title

      Apoptosis 14

      Pages: 1108-1120

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] mammalian target of rapamycin signaling potentiates the effects of all-trans retinoic acid to induce growth arrest and differentiation of human acute myelogenous leukemia cells.2009

    • Author(s)
      Nishioka C, Ikezoe T, Yang J, Gery S, Koeffler HP, Yokoyama A.
    • Journal Title

      Int J Cancer. 125

      Pages: 1710-1720

    • Related Report
      2010 Final Research Report
  • [Journal Article] Blockade of MEK signaling potentiates 5-Aza-2'-deoxycytidine-induced apoptosis and upregulation of leukemia cells.2009

    • Author(s)
      Nishioka C, Ikezoe T, Yang J, Komatsu N, Koeffler HP, Yokoyama A.
    • Journal Title

      Int J Cancer. 125

      Pages: 1168-1176

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] targeting polo-like kinase 1 in hematological malignancies.2009

    • Author(s)
      Ikezoe T, Yang J, Nishioka C, Takezaki Y, Tasaka T, Togitani K, Koeffler HP, Yokoyama A.
    • Journal Title

      Leukemia. 23

      Pages: 1564-1576

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of Aurora B kinase in non-Hodgkin lymphoma2009

    • Author(s)
      Ikezoe T
    • Journal Title

      Lab Invest 89

      Pages: 1364-1373

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel treatment strategy targeting polo-like kinase 1 in hematological malignancies2009

    • Author(s)
      Ikezoe T
    • Journal Title

      Leukemia 23

      Pages: 1564-1576

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of MEK signaling potentiates 5-Aza-2'-deoxycytidine-induced apoptosis and upregulation of p21(waf1)in acute myelogenous leukemia cells2009

    • Author(s)
      Nishioka C
    • Journal Title

      Int J Cancer 125

      Pages: 1168-1176

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of mammalian target of rapamycin signaling potentiates the effects of all-trans retinoic acid to induce growth arrest and differentiation of human acute myelogenous leukemia cells2009

    • Author(s)
      Nishioka C
    • Journal Title

      Int J Cancer 125

      Pages: 1710-1720

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of MEK signaling enhances the ability of cytarabine to induce growth arrest and apoptosis of acute myelogenous leukemia cells2009

    • Author(s)
      Nishioka C
    • Journal Title

      Apoptosis 14

      Pages: 1108-1120

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sunitinib, an orally available receptor tyrosine kinase inhibitor, induces monocytic differentiation of acute myelogenous leukemia cells that is enhanced by 1,25-dihydroxyvitamin D(3)2009

    • Author(s)
      Nishioka C
    • Journal Title

      Leukemia 23

      Pages: 2171-2173

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multitargeted tyrosine kinase inhibitor stimulates expression of IL-6 and activates JAK2/STAT5 signaling in acute myelogenous leukemia cells2009

    • Author(s)
      Nishioka C
    • Journal Title

      Leukemia 23

      Pages: 2304-2308

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cells.2008

    • Author(s)
      Nishioka C, et al.
    • Journal Title

      Leukemia 22

      Pages: 2159-69

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kill502, a novel multitargeted receptor tyrosine kinase inhibitor, induces growth arrest and apoptosis of human leukemia cells in vitro and in vivo.2008

    • Author(s)
      Nishioka C, et al.
    • Journal Title

      BLOOD 111

      Pages: 5086-92

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of MEK/ERK signaling synergistically potentiates histone deacetylase inhibitor-induced growth arrest, apoptosis and acetylation of histone H3 on p21wafl promoter in acute myelogenous leukemia cell.2008

    • Author(s)
      Nishioka C, et al.
    • Journal Title

      Leukemia 22

      Pages: 1449-52

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] P53 is critical for the Aurora B kinase inhibitor-mediated apoptosis in acute myelogenous leukemia cells. AACR 101st Annual Meeting 20102010

    • Author(s)
      Takayuki Ikezoe, Jing Yang, Chie Nishioka, Akihito Yokoyama.
    • Place of Presentation
      Washington, DC
    • Related Report
      2010 Final Research Report
  • [Presentation] An oncogenic role for CCAAT/enbancer binding protein beta in non-small cell lung cancer. AACR 101st Annual Meeting 20102010

    • Author(s)
      Nils H.Thoennissen, Gabriela B.Iwanski, Jianfei Ji,Takayuki Ikezoe, Kunik Lee, Yoshihiro Adachi,Tamotsu Takeuchi, Mutsuo Furihata, Dorothy J.Park, Adrian F.Gombart, H.P.Koffler.
    • Place of Presentation
      Washington, DC
    • Related Report
      2010 Final Research Report
  • [Presentation] CD34+/CD38- Leukemia Stem Cells Aberrantly Express CD82 Adhesion Molecule. 52nd ASH Annual Meeting and Exp2010

    • Author(s)
      Takayuki Ikezoe,Chie Nishioka, Jing Yang, Satoshi Serada, Tetsuji Naka, Akihito Yokoyama, Keiko Udaka.
    • Place of Presentation
      Orange County Convention Center, Orlando, FL
    • Related Report
      2010 Final Research Report
  • [Presentation] Recombinant Human Soluble Thrombomodulin Enhances the Anti-Fibrinolytic and Ant Effects of All-Trans Retinoic Acute Promyelocytic Leukemia Cells. 52nd ASH Annual Meeting and Exp2010

    • Author(s)
      Takayuki Ikezoe, Jing Yang, Chie Nishioka, Mayuka Isaka, Naomi Iwabu, Mizu Sakai, Ayuko Taniguchi, Kazuto Togitani, Goichi Honda, Akihito Yokoyama.
    • Place of Presentation
      Orange County Convention Center, Orlando, FL
    • Related Report
      2010 Final Research Report
  • [Presentation] CD34+/CD38- leukemia stem cells aberrantly express CD82 adhesion molecule2010

    • Author(s)
      Ikezoe T
    • Organizer
      第52回米国血液学会総会
    • Place of Presentation
      米国フロリダ州オーランド
    • Related Report
      2010 Annual Research Report
  • [Presentation] Development of a novel treatment strategy targeting JAK2 in acute myelogenous leukemia2009

    • Author(s)
      Kojima S
    • Organizer
      American Society of Hematology
    • Place of Presentation
      Ernest N.Morial Convention センター 米国 ニューオーリンズ
    • Year and Date
      2009-12-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] Inhibition of STAT5 by IL-1β or the inhibitor of janus kinases stimulates dormant human leukemia stem cells and sensitizes them to anti-leukemia agents2009

    • Author(s)
      Ikezoe T
    • Organizer
      American Society of Hematology
    • Place of Presentation
      Ernest N.Morial Convention センター 米国 ニューオーリンズ
    • Year and Date
      2009-12-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] Inhibition of STAT5 by IL-1β of the Inhibitor of Janus kinases Stimulates Dormant Humon Leukemia Stem Cells and Sensitizes Them to Anti-Leukemia Agents. 51ST ASH ANNUAL MEETING AND EXPOSITION2009

    • Author(s)
      Takayuki Ikezoe, Yang Jing, Chie Nisioka, Sinsuke Kojima, Asako Takeuchi, Akihito Yokoyama.
    • Place of Presentation
      NEW ORLEANS
    • Related Report
      2010 Final Research Report
  • [Presentation] Development of a Novel Treatment Strategy Targeting JAK2 in Acute myelogenous Leukemia. 51ST ASH ANNUAL MEETING AND EXPOSITION2009

    • Author(s)
      Sinsuke Kojima, Takayuki Ikezoe, Mutsuo Furihata, Jing Yang, Chie Nisioka, Asako Takeuchi, Mayuka Isaka, H.Phillip Koeffler, Akihito Yokoyama.
    • Place of Presentation
      NEW ORLEANS
    • Related Report
      2010 Final Research Report
  • [Presentation] Analysis of Aurora B kinase in non-Hodgkin's lymphoma2008

    • Author(s)
      Ikezoe T
    • Organizer
      American Association of Hematology
    • Place of Presentation
      米国サンフランシスコ
    • Year and Date
      2008-12-06
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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