骨髓增生异常综合征(MDS)是一组异质性克隆性疾患,迄今其病因和发病机制尚知之不多.近年来发现MDS患者存在表现遗传调节子(epigenetic regulator)基因如TET2、ASXL1、EZH2、DNMT3A、UTX等突变,其中TET2基因可能与5-羟甲基胞嘧啶的形成所致去甲基化有关,它是目前在MDS中发现突变率最高的基因,可能起到抑癌基因的作用；ASXL1基因编码蛋白是trithorax和Polycomb的增强子,ASXL1基因异常引起MDS发生可能不仅仅是功能缺失所致,而涉及其他更复杂的机制如异常功能的获得、过度表达等；EZH2基因编码蛋白为一组蛋白甲基转移酶,其表达水平在多种肿瘤组织中异常增高,支持其具有癌基因的活性,另有研究发现该基因突变后功能缺失,提示EZH2在髓系肿瘤发生中也可起到抑癌基因的作用；DNMT3A属于DNA甲基转移酶(DNMT)基因家族,可能和MDS异常甲基化状态有关；UTX基因编码蛋白为一种组蛋白去甲基化酶,可影响细胞增殖和决定细胞命运(cell fate),近年来在多种肿瘤中检测到该基因失活突变.这些基因突变也许参与了MDS发生,本文就这方面研究进展做一综述.%The myelodysplasic syndrome (MDS) is a group of heterogeneous clonal disorders. So far, the etiology and pathogenesis of MDS is poorly understood. Recently, more and more epigenetic regulator gene such as TET2, ASXL1 ,EZH2 ,DNMT3A and UTX mutations were detected in patients with MDS.TET2 may convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC) . TET2 is the most frequently mutated gene in MDS known so far and it may act as tumor-suppressor gene. ASXL1 belongs to the enhancer of tri thorax and Poly comb ( ETT") gene group. MDS phenotypes may be caused not only by loss-of-function of ASXL1 but also by gain-of-function mutations, overexpression of this gene and so on. EZH2 is a kind of histone methyltransferase. EZH2 is frequently over-expressed in a wide variety of cancerous tissue types, which reveals it has oncogenic activity . While, defined mutations resulted in dysfunction of histone methyltransferase activity, suggesting that EZH2 acts as a tumor suppressor for myeloid malignancies. DNMT3A belongs to the DNA methytransferases (DNMT) gene family. It may be correlated with abnomal methylation status in patients with MDS. UTX coding protein is a histone demethylase, and UTX can affect cell proliferation as well as cell fate decision. Inactivating UTX mutations are found in multiple cancer types recently. These gene mutations may play key roles in the pathogenesis of MDS, which are summarized in this review.
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