Role of epigenetic dysregulation in the pathogenesis of hematological malignancies

2014 Fiscal Year Final Research Report

• Project/Area Number: 24249054
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Chiba University
• Principal Investigator: IWAMA Atsushi 千葉大学, 医学(系)研究科(研究院), 教授 (70244126)
• Co-Investigator(Kenkyū-buntansha): SASHIDA Goro 熊本大学, 国際先端医学研究機構, 特別招聘準教授 (70349447)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: エピジェネティクス / 造血器腫瘍 / ポリコーム群遺伝子 / 骨髄異形成症候群

Outline of Final Research Achievements

We demonstrated that the polycomb gene Ezh2 is required to promote MLL-AF9-driven acute myeloid leukemia (AML) in mice (Blood 120:1107, 2012). In contrast, we also found that the hematopoietic-specific deletion of Ezh2 in mice induced heterogeneous hematopoietic malignancies, including myelodysplastic syndrome (MDS), MDS/myeloproliferative neoplasms (MDS/MPN), and T-ALL after a long latency. Furthermore, the concurrent depletion of Ezh2 and Tet2 in mice markedly accelerated the development of MDS and MDS/MPN and Ezh2 loss significantly promoted RUNX1S291fs-induced MDS (J Exp Med 210:2627, 2013; Nat Commun 5:4177, 2014). These findings support the tumor suppressor function of EZH2 in the context of myelodysplastic disorders and well correspond to the identification of recurrent inactivating mutations in EZH2 in patients with MDS, MPN, MDS/MPN, and T-ALL.

Free Research Field

血液内科学