Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan-Kettering Cancer Center, 408 East 69th Street, New York, NY 10065, USA.
Curr Hematol Malig Rep. 2012 Mar;7(1):34-42. doi: 10.1007/s11899-011-0105-y.
The discovery of mutations activating JAK-STAT signaling in the majority of patients with myeloproliferative neoplasms (MPNs) led to identification of tyrosine kinase activation as the common predominant mechanism driving MPN pathogenesis. Nevertheless, the existence of additional genetic events that modify the MPN phenotype, predate JAK2 mutations, or contribute to leukemic transformation of MPNs was suspected. Recent advances in genomic technologies have led to the discovery of mutations in a number of epigenetic modifiers in patients with MPNs, including mutations in TET2, ASXL1, IDH1, IDH2, and EZH2. In addition to mutation, alterations in the expression or activity of chromatin-modifying/reading proteins PRMT5 and L3MBTL1 have been found to be important in MPN development. Moreover, the JAK2 mutation itself recently has been shown to directly affect histone post-translational modifications. This article reviews the clinical and functional implications of epigenetic alterations in the pathogenesis of MPNs.
大多数骨髓增殖性肿瘤（MPN）患者中 JAK-STAT 信号通路的突变的发现导致了酪氨酸激酶激活作为驱动 MPN 发病机制的共同主要机制的鉴定。然而，存在额外的遗传事件会改变 MPN 表型，早于 JAK2 突变，或有助于 MPN 的白血病转化，这一点是可疑的。基因组技术的最新进展导致在 MPN 患者中发现了许多表观遗传修饰因子的突变，包括 TET2、ASXL1、IDH1、IDH2 和 EZH2 的突变。除了突变之外，染色质修饰/读取蛋白 PRMT5 和 L3MBTL1 的表达或活性的改变也被发现对 MPN 的发展很重要。此外，JAK2 突变本身最近也被证明会直接影响组蛋白的翻译后修饰。本文综述了表观遗传改变在 MPN 发病机制中的临床和功能意义。
