骨髓增生异常综合征剪接体突变的研究进展

Research progress on spliceosome mutations in myelodysplastic syndromes

研究发现剪接体突变在骨髓增生异常综合征(myelodysplastic syndrome,MDS)疾病的发生发展中发挥重要作用,其突变基因包括SF3B1、U2AF1(U2AF35)、SRSF2、ZRSR2、PRPF40B、SF1、SF3A1和U2AF2等,突变基因(45%~85%)发生在mRNA剪接过程中的3'剪接位点,主要表现为杂合性错义突变。了解RNA剪接对MDS的靶向治疗及预后具有指导作用。本文就剪接体相关突变基因在MDS中的致病机制、靶向治疗及临床预后等进行综述。

Spliceosomal dysfunction plays a major role in pathogenesis of myelodysplastic syndrome（MDS）. Splicing factor somat mutations, including SF3B1, U2AF1（U2AF35）, SRSF2, ZRSR2, PRPF40 B, SF1, SF3A1, and U2AF2, comprise a common（45%–85%） clas of mutated genes in MDS. These genes exist in a mutually exclusive manner at the 3’splice site of mRNA processing and are predom nantly heterozygous and missense. RNA splicing might have therapeutic and prognosis values in MDS. This review mainly describes th pathogenesis of common splicing factor gene mutations in MDS and discusses possible therapeutic implications, clinical analysis, an prognosis.