骨髓增生异常综合征患者对去甲基化药物耐药机制的新进展

Advances on resistance mechanisms of hypomethylating agents in patients with myelodysplastic syndrome

骨髓增生异常综合征(MDS)是一组异质性的克隆性髓样干细胞疾病,以全血细胞减少、向急性髓细胞白血病(AML)转化风险高为特点。目前,去甲基化药物(HMA)已广泛用于MDS治疗,在临床试验和实际应用中均展现良好疗效,但是HMA耐药现象普遍存在,并且MDS患者发生HMA耐药预后较差。笔者通过对HMA作用机制,以及影响HMA的药物代谢因素、免疫检查点通路(ICP)表达上调、白血病干/祖细胞(LSPC)无法被完全消除等HMA耐药机制的最新研究进展进行阐述,旨在探究MDS患者发生HMA耐药的可能机制及其解决方法。

Myelodysplastic syndrome(MDS)consists of a group of heterogeneous clonal myeloid stem cell diseases characterized by pancytopenia and high-risk of transformation to acute myeloid leukemia(AML).At present,the hypomethylating agents(HMA)are widely used in the treatment of MDS,which show good therapeutic effects in clinical trials and practical applications,but the phenomenon of HMA resistance is almost universal,and the prognosis of patients with HMA resistance is often poor.This article explains the advance on mechanisms of HMA,and the resistance mechanisms of HMA which include the drug metabolism factors that affect HMA,the up-regulation expression of immune checkpoint pathway(ICP),and the imcompletely eliminate of leukemia stem/progenitor cells(LSPC),in order to explore the possible mechanisms and solutions methods of HMA resistance in MDS patients.