Molecular mechanism of refractoriness of myeloma mediated by adhesion molecules
| Project/Area Number |
23591409
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
IMAI Yoichi 東京女子医科大学, 医学部, 講師 (10345209)
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| Co-Investigator(Renkei-kenkyūsha) |
MARU Yoshiro 東京女子医科大学, 医学部, 教授 (00251447)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 血液腫瘍学 / 多発性骨髄腫 / 接着分子 / カルシニューリン / 国際情報交換 / インテグリン / CXCR4 / HDAC阻害剤 / HOXA9 / 増殖抑制 / アポトーシス |
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| 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.
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Report
(4 results)
Research Products
(25 results)
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[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
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Journal Title
European Journal of Immunology
Volume: 42
Pages: 1044-1050
Related Report
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[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
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Journal Title
Journal of Experimental Medicine
Volume: 208
Pages: 2403-2416
Related Report
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[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
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Journal Title
Blood
Volume: 118
Pages: 6626-6637
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[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
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Journal Title
Blood
Volume: 117
Pages: 3617-3628
Related Report
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