儿童急性髓系白血病的表观遗传学及治疗研究进展

Advances in epigenetics and treatment of childhood acute myeloid leukemia

表观遗传学改变包括染色体易位、多梳蛋白(polycomb)功能和非编码RNA异常等,对儿童急性髓系白血病(acute myeloid leukemia,AML)基因组的研究表明,这些相关异常在其发病中起重要作用,并且表观遗传异质性与AML预后不良及易复发相关。目前儿童AML的总体生存率(overall survival,OS)有所提高,但难治性或复发AML(refractory/relapsed acute myeloid leukemia,r/r AML)患儿的预后及治疗效果仍然不佳,表观遗传学相关的治疗方法有望进一步提高AML的疗效。儿童AML表观遗传学异常的特点与成人不同。针对表观遗传学改变的相关药物,如DNA甲基转移酶抑制剂、IDH抑制剂等已经用于儿童AML的治疗。该文拟就儿童AML中表观遗传调控异常的研究及临床应用方面的相关进展进行综述。

Epigenetic alterations include chromosome translocation,polycomb function and non-coding RNA abnormalities,and etc.A study on genome of childhood acute myeloid leukemia(AML)in children has shown that these abnormalities play an important role in the pathogenesis of AML,and epigenetic heterogeneity is associated with poor prognosis and relapse of AML.Presently,the overall survival(OS)for AML in children has been improved,but for the refractory/relapsed acute myeloid leukemia(r/r AML),the prognosis or curative effect remains poor.The curative effect is expected to be improved by epigenetics related therapies.A large number of studies have found that the epigenetic abnormalities of AML in children are different from those in adults.Some drugs targeting epigenetic alternations,such as DNA methyltransferase inhibitor and IDH inhibitor,have been used to treat AML in children.This paper aims to review the epigenetic regulation abnormalities in children with AML and the progress in relevant clinical applications.