U2AF1突变对骨髓增生异常综合征预后及治疗影响的研究现状

Research status on U2AF1 mutation in prognosis and treatment of myelodysplastic syndromes

骨髓增生异常综合征(MDS)是一组起源于骨髓造血干/祖细胞的恶性克隆性疾病,其主要特征是骨髓一系或多系病态造血,外周血细胞减少,并且向急性髓细胞白血病(AML)转化风险极高。MDS发病机制与体细胞基因突变、表观遗传学改变、免疫系统与骨髓微环境调节异常等因素密切相关。多项研究表明,基因突变是MDS患者预后的影响因素,但是目前单基因突变并未纳入MDS预后评分系统。MDS患者的U2AF1突变率较高,其作用机制主要为影响RNA剪接体对前体信使RNA(pre-mRNA)的3′剪接位点(SS)识别过程,进而生成异常mRNA,造成染色体不稳定。笔者拟就近年U2AF1突变对MDS的预后影响和治疗进展进行阐述,为探索伴U2AF1突变MDS患者的新治疗方向提供理论依据。

Myelodysplastic syndromes(MDS)are a group of malignant clonal diseases originating from hematopoietic stem/progenitor cells of bone marrow,which are characterized by one or more myelopoietic lines of bone marrow,peripheral blood cytopenia and high risk of transformation to acute myeloid leukemia(AML).The pathogenesis of MDS is closely related to somatic gene mutation,epigenetic changes,abnormal immune system and bone marrow microenvironment regulation.At present,the factor of single gene mutation is not included in the MDS prognosic scoring system,but a number of studies have shown that gene mutation is an independent factor affecting the prognosis and survival of MDS patients.The mutation rate of U2AF1 gene in MDS is high,and its mechanism is mainly to affect the 3′splice site(SS)recognition process of precursor messenger RNA(pre-mRNA)by RNA splicing body,and then generate abnormal mRNA,resulting in chromosome instability.This article reviews the prognostic effects of U2AF1 gene mutation on MDS and its treatment progress in recent years,so as to provide theoretical basis for the new treatment direction of MDS patients with U2AF1 gene mutation.