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2013 Fiscal Year Final Research Report

Molecular mechanism of refractoriness of myeloma mediated by adhesion molecules

Research Project

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Project/Area Number 23591409
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionTokyo Women's Medical University

Principal Investigator

IMAI Yoichi  東京女子医科大学, 医学部, 講師 (10345209)

Co-Investigator(Renkei-kenkyūsha) MARU Yoshiro  東京女子医科大学, 医学部, 教授 (00251447)
Project Period (FY) 2011 – 2013
Keywords血液腫瘍学
Research Abstract

Multiple myeloma is one of incurable hematological malignancies. We revealed that functional inhibition of integrin and histone deacetylase (HDAC) blocks proliferation and induces apoptosis in myeloma cells. We discovered that MLL-HOXA9 and PPP3CA, alfa subunit of calcineurin, are inhibited by HDAC inhibitors. We revealed that MLL and PPP3CA are protected from protein degradation by HSP90. HDAC inhibitors induce degradation of MLL and PPP3CA through inhibition of chaperone function of HSP90. It was shown that PPP3CA plays important roles in maintenance of viability of myeloma cells in vitro and in vivo. In clinical samples, PPP3CA expression was high in advanced disease. Osteoclasts formation is essential for osteolytic disease of multiple myeloma. PPP3CA was necessary for formation of osteoclasts and HDAC inhibitors were shown to inhibit osteoclasts formation.

  • Research Products

    (16 results)

All 2014 2013 2012 2011

All Journal Article (13 results) Presentation (2 results) Book (1 results)

  • [Journal Article] A case report of donor cell-derived leukemia after cord blood transplantation and a review of the literature : differences from bone marrow as the transplanted source2014

    • Author(s)
      Shiozaki H, Yoshinaga K, Kondo T, Imai Y, Shiseki M, Mori N, Teramura M, Motoji T
    • Journal Title

      Bone Marrow Transplantation

      Volume: 49 Pages: 102-109

  • [Journal Article] Identification of calcineurin as a novel therapeutic target in multiple myeloma2013

    • Author(s)
      Imai Y, Ohta E, Wang Y, Kitagawa Y, Ding Y, Yamada O, Maru Y, Motoji T
    • Journal Title

      Clinical Lymphoma, Myeloma, & Leukemia

      Volume: 13 Pages: S47

  • [Journal Article] Transient lupus anticoagulant with a prolonged activated partial thromboplastin time secondary to cytomegalovirus-related infectious mononucleosis2013

    • Author(s)
      Shimura H, Imai Y, Ieko M, Shiseki M, Mori N, Teramura M, Motoji T
    • Journal Title

      Annals of Hematology

      Volume: 2 Pages: 143-144

  • [Journal Article] MLL-HOXA9 and calcineurin are novel therapeutic targets in multiple myeloma2012

    • Author(s)
      Imai Y, Ohta E, Wang Y, Kitagawa Y, Ding Y, Yamada O, Maru Y, Motoji T
    • Journal Title

      American Society of Hematology annual meeting abstracts

      Volume: 120 Pages: 4007

  • [Journal Article] Multiple phosphorylation sites are important for RUNX1 activity in early hematopoiesis and T-cell differentiation2012

    • Author(s)
      Yoshimi M, Goyama S, Kawazu M, Nakagawa M, Ichikawa M, Imai Y, Kumano K, Asai T, Mulloy JC, Kraft AS, Takahashi T, Shirafuji N, Kurokawa M
    • Journal Title

      European Journal of Immunology

      Volume: 42 Pages: 1044-1050

  • [Journal Article] The effect of iron overload and chelation on erythroid differentiation2012

    • Author(s)
      Taoka K, Kumano K, Nakamura F, Hosoi M, Goyama S, Imai Y, Hangaishi A, Kurokawa M
    • Journal Title

      International Journal of Hematology

      Volume: 95 Pages: 149-159

  • [Journal Article] Combined romiplostim and intravenous immunoglobulin therapy increased platelet count, facilitating splenectomy in a patient with refractory immune thrombocytopenic purpura unresponsive to monotherapy2012

    • Author(s)
      Mitsuhashi K, Ishiyama M, Imai Y, Shiseki M, Mori N, Teramura M, Seshimo A, Motoji T
    • Journal Title

      British Journal of Haematology

      Volume: 158 Pages: 798-800

  • [Journal Article] Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity2011

    • Author(s)
      Kataoka K, Sato T, Yoshimi A, Goyama S, Tsuruta T, Kobayashi H, Shimabe M, Arai S, Nakagawa M, Imai Y, Kumano K, Kumagai K, Kubota, N, Kadowaki T, Kurokawa M
    • Journal Title

      Journal of Experimental Medicine

      Volume: 208 Pages: 2403-2416

  • [Journal Article] AML1/RUNX1 functions as a cytoplasmic attenuator of NF-kB signaling in the repression of myeloid tumors2011

    • Author(s)
      Nakagawa M, Shimabe M, Watanabe-Okochi N, Arai S, Yoshimi A, Shinohara A, Nishimoto N, Kataoka K, Sato T, Kumano K, Nannya Y, Ichikawa M, Imai Y, Kurokawa M
    • Journal Title

      Blood

      Volume: 118 Pages: 6626-6637

  • [Journal Article] Loss of AML1/Runx1 accelerates the development of MLL-ENL leukemia through down-regulation of p19^<ARF>2011

    • Author(s)
      Nishimoto N, Arai S, Ichikawa M, Nakagawa M, Goyama S, Kumano K, Takahashi T, Kamikubo Y, Imai Y, Kurokawa M
    • Journal Title

      Blood

      Volume: 118 Pages: 2541-2550

  • [Journal Article] The negative impact of female donor/male recipient combination in allogeneic hematopoietic stem cell transplantation depends on disease risk2011

    • Author(s)
      Nannya Y, Kataoka K, Hangaishi A, Imai Y, Takahashi T, Kurokawa M
    • Journal Title

      Transplant International

      Volume: 24 Pages: 469-476

  • [Journal Article] Evi-1 is a transcriptional target of mixed-lineage leukemia oncoproteins in hematopoietic stem cells2011

    • Author(s)
      Arai S, Yoshimi A, Shimabe M, Ichikawa M, Nakagawa M, Imai Y, Goyama S, Kurokawa M
    • Journal Title

      Blood

      Volume: 117 Pages: 6304-6314

  • [Journal Article] Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins2011

    • Author(s)
      Yoshimi A, Goyama S, Watanabe-Okochi N, Yoshiki Y, Nannya Y, Nitta E, Arai S, Sato T, Shimabe M, Nakagawa M, Imai Y, Kitamura T, Kurokawa M
    • Journal Title

      Blood

      Volume: 117 Pages: 3617-3628

  • [Presentation] Identification of calcineurin as a novel therapeutic target in multiple myeloma2013

    • Author(s)
      Imai Y, Ohta E, Wang Y, Kitagawa Y, Ding Y, Yamada O, Maru Y, Motoji T
    • Organizer
      14th International Myeloma Workshop
    • Place of Presentation
      Kyoto
    • Year and Date
      2013-04-04
  • [Presentation] MLL-HOXA9 and calcineurin are novel therapeutic targets in multiple myeloma2012

    • Author(s)
      Imai Y, Ohta E, Wang Y, Kitagawa Y, Ding Y, Yamada O, Maru Y, Motoji T
    • Organizer
      54th American Society of Hematology Annual Meeting
    • Place of Presentation
      Atlanta, December
    • Year and Date
      20121000
  • [Book] 多発性骨髄腫発生病理とmixed-lineage leukemia (MLL)タンパク2014

    • Author(s)
      今井陽一、太田瑛里
    • Total Pages
      1047-1051
    • Publisher
      日本臨床第72巻・第6号

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Published: 2015-07-16  

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