Conway O'Brien Emma, Prideaux Steven, Chevassut Timothy
Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton BN1 9PS, UK.
Adv Hematol. 2014;2014:103175. doi: 10.1155/2014/103175. Epub 2014 Mar 23.
Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Certain cytogenetic and molecular genetic mutations are recognized to have an impact on prognosis, leading to their inclusion in some prognostic stratification systems. Recently, the advent of high-throughput whole genome or exome sequencing has led to the identification of several novel recurrent mutations in AML, a number of which have been found to involve genes concerned with epigenetic regulation. These genes include in particular DNMT3A, TET2, and IDH1/2, involved with regulation of DNA methylation, and EZH2 and ASXL-1, which are implicated in regulation of histones. However, the precise mechanisms linking these genes to AML pathogenesis have yet to be fully elucidated as has their respective prognostic relevance. As massively parallel DNA sequencing becomes increasingly accessible for patients, there is a need for clarification of the clinical implications of these mutations. This review examines the literature surrounding the biology of these epigenetic modifying genes with regard to leukemogenesis and their clinical and prognostic relevance in AML when mutated.
急性髓系白血病（AML）是一种基因异质性疾病。某些细胞遗传学和分子遗传学突变被认为会影响预后，从而被纳入一些预后分层系统。最近，高通量全基因组或外显子组测序技术的出现，使得在AML中鉴定出了几种新的复发性突变，其中许多突变涉及与表观遗传调控相关的基因。这些基因尤其包括与DNA甲基化调控有关的DNMT3A、TET2和IDH1/2，以及与组蛋白调控有关的EZH2和ASXL-1。然而，将这些基因与AML发病机制联系起来的精确机制及其各自的预后相关性尚未完全阐明。随着大规模平行DNA测序技术越来越容易应用于患者，有必要阐明这些突变的临床意义。这篇综述探讨了围绕这些表观遗传修饰基因在白血病发生方面的生物学特性，以及它们在AML中发生突变时的临床和预后相关性的相关文献。
