急性髓细胞白血病的表观遗传学异常改变及其靶向治疗的研究进展

目前,由于传统化疗的局限性,急性髓细胞白血病(AML)的治疗一直未能取得突破性的进展,特别是如何提高复发/难治性患者的疗效已成为AML临床治疗中一个亟待解决的难题.近年来,随着对AML分子生物学研究的不断深入,一些具有预后意义的分子遗传学改变有望作为AML危险度分层的指标以及治疗靶点,而引起学术界的广泛关注.有关AML分子靶向药物治疗的研究层出不穷,其中针对AML表观遗传学异常改变的治疗研究已经取得了较大的进展.表观遗传学改变与基因突变有重要的区别,即表观遗传学改变是可逆的,通过使用针对相应的表观遗传学异常改变的药物可使沉默的抑癌基因重新表达.目前,应用于AML临床治疗的针对表观遗传学异常改变的药物主要包括DNA去甲基化药物与组蛋白去乙酰化酶抑制剂,以及二者的联合应用.针对AML表观遗传学异常改变的治疗方案有望成为中、高危AML患者,尤其是不能耐受化疗的老年患者的治疗选择之一.笔者拟就AML的表观遗传学改变,以及其靶向治疗的研究进展进行综述.

Research progress of epigenetic regulation and its targeted therapeutics in acute myeloid leukemia

The treatment for acute myeloid leukemia (AML) has not been able to make breakthrough in the last few years due to the limitations of conventional chemotherapy,especially on how to improve the efficacy of recurrent or refractory AML patients,which has become a problem to be solved urgently in clinical.In recent years,with further understanding of molecular biology of AML,some molecular genomic changes with prognostic implications are potential biomarkers for risk stratification and targeted therapy,which caused widespread concern.Researches of the molecular targeted agents of AML are emerging,among them,the epigenetic targeting therapy has made great progress.Epigenetic regulations are reversible which is different from gene changes.Those silent tumor suppressor genes would express again by using appropriate epigenetic agents.The current application of epigenetic drugs mainly includes DNA demethylation agents,histone deacetylase inhibitors and the combination of them.Epigenetics therapies are expected to be treatment options in high-risk AML patient,especially for elderly patients who can't tolerate intensive chemotherapy.This article reviews literatures on research progress of epigenetic regulation and its targeted therapeutics in AML.