| Project/Area Number |
26860719
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Chiba University |
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Principal Investigator |
MIMURA Naoya 千葉大学, 医学部附属病院, 助教 (00422220)
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| Co-Investigator(Renkei-kenkyūsha) |
IWAMA Atsushi 千葉大学, 大学院医学研究院, 教授 (70244126)
OHSHIMA Motohiko 千葉大学, 大学院医学研究院, 特任助教 (70506287)
NAKAJIMA Yaeko 千葉大学, 大学院医学研究院, 日本学術振興会特別研究員RPD (50749497)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 多発性骨髄腫 / エピジェネティック異常 / ヒストンメチル化 / EZH2阻害薬 / EZH2 / EZH2阻害剤 / プロテアソーム阻害剤 |
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| Outline of Final Research Achievements |
In this study, we focus on EZH2 and its homolog EZH1, both of which induce H3K27me3 as the catalytic components of PRC2, resulting in repressed transcription of target genes. In MM, EZH2 overexpression and inactivating mutations of UTX, a histone demethylase which removes methyl groups of H3K27, suggest an oncogenic function of H3K27me3. We demonstrate not only the anti-MM effects of the dual inhibitor of EZH2 and EZH1, UNC1999, both in vitro and in vivo, but also the combination effects with bortezomib. Our findings provide the rationale for this novel strategy; dual inhibition of EZH2 and EZH1 in combination with proteasome inhibition.
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