Epigenetic dysregulation in myelodysplastic syndromes in the absence of Ezh2

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461396
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kumamoto University
• Principal Investigator: SASHIDA GORO 熊本大学, 国際先端医学研究機構, 特別招聘教授 (70349447)
• Co-Investigator(Renkei-kenkyūsha): IWAMA Atsushi 千葉大学, 大学院医学研究院, 教授 (70244126)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 骨髄異形成症候群 / 慢性骨髄増殖性腫瘍 / 骨髄線維症 / エピゲノム / ポリコーム複合体 / TET2 / RUNX1 / JAK2

Outline of Final Research Achievements

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease characterized by impaired hematopoiesis and an increased risk of transformation to acute myeloid leukemia (AML). Epigenetic regulators including TET2, DNMT3A and EZH2 are often mutated in patients with MDS. Recently, exome sequencing of blood cells from aged people without hematological malignancies demonstrated the presence of clonal hematopoiesis as given myeloid malignancies-associated mutations such as TET2 and DNMT3A. In this study, I have unveiled molecular mechanisms of how accumulation of epigenetic alterations and genetic mutations including EZH2 promote the development of MDS and hematological malignancies by utilizing Ezh2 conditional knockout mice. In addition, I have provided a basis for specific rational epigenetic therapy for myeloid malignancies with Ezh2 dysfunction.

Free Research Field

造血器腫瘍の病態基盤解明