DNA Methyltransferases in Hematologic Malignancies

被引：38

作者：

Li, Keqin Kathy ^{[1
]}

Luo, Liu-Fei ^{[1
]}

Shen, Yang ^{[1
]}

Xu, Jie ^{[1
]}

Chen, Zhu ^{[1
]}

Chen, Sai-Juan ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, State Key Lab Med Genom,Shanghai Inst Hematol, Shanghai 200025, Peoples R China

来源：

SEMINARS IN HEMATOLOGY | 2013年 / 50卷 / 01期

基金：

中国国家自然科学基金;

关键词：

ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; DE-NOVO METHYLATION; DNMT3A MUTATIONS; SOMATIC MUTATIONS; CANCER GENOME; HEMATOPOIETIC STEM; ACQUIRED MUTATIONS; EPIGENETIC EVENTS; GENE EZH2;

D O I：

10.1053/j.seminhematol.2013.01.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

DNA methyltransferases (DNMTs) are the key enzymes for genome methylation, which plays an important role in epigenetically regulated gene expression and repression. Mouse models with conditional knockout of the DNA methyltransferase 1 (DNMT1) and DNA methyltransferase 3A (DNMT3A) genes have revealed a role of DNA methylation in mediating the self-renewal and differentiation of normal hematopoietic stem cells (HSCs) and the leukemia stem cells (LSCs). Recently, various mutations of DNMT3A and other DNA methylation regulators have been identified in hematologic malignancies. Functional analysis of these mutations may lead to a better understanding of the disease mechanisms, and even the discovery of new biomarkers and/or drug targets, as well as more rational design of therapeutic regimens. Moreover, DNMTs inhibitors as epigenetic drugs have already been approved by US Food and Drug Administration for clinical use and some clinical trials are currently underway in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). This review focuses on the biology of DNMTs with regard to epigenetic regulation, HSC renewal/differentiation, and drug discovery for targeted therapy, and delineates the latest studies that have been conducted to unfold the relationship between aberrant DNMTs and hematologic malignancies. Semin Hematol 50:48-60. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：48 / 60

页数：13

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