Analysis of pathogenic mechanisms of myelodysplastic syndrome by deregulation of histone H3K27

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293227
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Hiroshima University
• Principal Investigator: Honda Hiroaki 広島大学, 原爆放射線医科学研究所, 教授 (40245064)
• Co-Investigator(Kenkyū-buntansha): 上田 健 広島大学, 原爆放射線医科学研究所, 助教 (60585149) ; 本田 善一郎 お茶の水女子大学, 保健管理センター, 教授 (70238814) ; 稲葉 俊哉 広島大学, 原爆放射線医科学研究所, 教授 (60281292)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ヒストン修飾 / ポリコーム複合体 / EED / コンディショナルノックアウトマウス / 骨髄異形成症候群 / 白血病

Outline of Final Research Achievements

EED is a component of polycomb repressive complex 2 and is found to be mutated in samples of myelodysplastic syndrome (MDS). We generated conditional heterozygous mice for Eed (Eed+/Δ) and found that Eed+/Δ mice exhibited hematopoietic abnormalities resembling MDS. In addition, in a competitive repopulation assay, Eed+/Δ hematopoietic stem cells (HSCs) showed higher chimerism than control HSCs, and by retrovirus-mediated insertional mutagenesis, Eed+/Δ mice exhibited higher incidence of leukemia than control mice. These results indicate that heterozygosity of Eed induced MDS and rendered high susceptibility to leukemia by enhancing proliferative activity of HSCs.

Free Research Field

血液内科学