Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA.
Nat Rev Cancer. 2012 Sep;12(9):599-612. doi: 10.1038/nrc3343. Epub 2012 Aug 17.
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.
最近的基因组研究已经鉴定出髓系恶性肿瘤（包括骨髓增生性肿瘤、骨髓增生异常综合征和急性髓系白血病）患者中新型的反复出现的体细胞突变。在某些情况下，这些突变发生在已知在造血祖细胞中调节染色质和/或甲基化状态的基因中，在其他情况下，遗传和功能研究已经阐明了特定突变在改变髓系恶性肿瘤中的表观遗传模式方面的作用。在这篇综述中，我们讨论了最近的遗传和功能数据，这些数据表明表观遗传修饰因子的突变，包括 TET2、IDH1、IDH2、ASXL1、EZH2 和 DNMT3A，与 MPN、MDS 和 AML 的发病机制有关，并讨论了这些知识如何带来新的临床、生物学和治疗见解。
