The role of mutations in epigenetic regulators in myeloid malignancies

被引：554

作者：

Shih, Alan H. ^{[1
,2
]}

Abdel-Wahab, Omar ^{[1
,2
]}

Patel, Jay P. ^{[1
]}

Levine, Ross L. ^{[1
,2
]}

机构：

[1] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY USA

[2] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Leukemia Serv, Dept Med, New York, NY USA

来源：

NATURE REVIEWS CANCER | 2012年 / 12卷 / 09期

基金：

美国国家卫生研究院;

关键词：

CHRONIC MYELOMONOCYTIC LEUKEMIA; HISTONE METHYLTRANSFERASE EZH2; ACUTE PROMYELOCYTIC LEUKEMIA; HEMATOPOIETIC STEM-CELLS; DNMT3A MUTATIONS; PROGNOSTIC-SIGNIFICANCE; SOMATIC MUTATIONS; ADULT PATIENTS; ONCOMETABOLITE; 2-HYDROXYGLUTARATE; ESSENTIAL THROMBOCYTHEMIA;

D O I：

10.1038/nrc3343

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Recent genomic studies have identified novel recurrent somatic mutations in patients with myeloid malignancies, including myeloproliferative neoplasms (MPNs), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). In some cases these mutations occur in genes with known roles in regulating chromatin and/or methylation states in haematopoietic progenitors, and in other cases genetic and functional studies have elucidated a role for specific mutations in altering epigenetic patterning in myeloid malignancies. In this Review we discuss recent genetic and functional data implicating mutations in epigenetic modifiers, including tet methylcytosine dioxygenase 2 (TET2), isocitrate dehydrogenase 1 (IDH1), IDH2, additional sex combs-like 1 (ASXL1), enhancer of zeste homologue 2 (EZH2) and DNA methyltransferase 3A (DNMT3A), in the pathogenesis of MPN, MDS and AML, and discuss how this knowledge is leading to novel clinical, biological and therapeutic insights.

引用

收藏

页码：599 / 612

页数：14

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