慢性淋巴细胞白血病中的RNA可变剪接异常及功能分析OA

Objective To investigate aberrant alternative splicing and splicing factor-mediated regulation in chronic lymphocytic leukemia(CLL).Methods High-throughput transcriptome sequencing was performed on peripheral blood mononuclear cells from 3 healthy controls(HC),and public data from 2 CLL patients and 6 patients treated with voruciclib(PT)were included.The rMATS software was used to quantify alternative splicing events(ASEs)and identify differential alternative splicing events(DASEs).The expression changes and self-splicing alterations of splicing factors(SFs)were analyzed.Results A total of 12 933,32 908,and 32 862 ASEs were identified in HC,CLL,and PT samples,respectively,with skipped exons being the predominant type.4 134 DASEs were detected in CLL vs.HC,among which 69.5%corresponded to decrease in percent spliced-in(PSI).Complex interactions were observed between PSI changes and gene expression alterations.Splicing factors exhibited alterations at both ex-pression and PSI levels in CLL.In total,330 DASEs displayed opposite ΔPSI trends between disease progression and treatment response including 276 events with a"PSI decrease in disease-PSI increase after treatment"pattern enriched in the cell cycle and DNA repair processes,and 54 events with a"PSI increase in disease-PSI decrease after treatment"pattern enriched in autophagy and phosphorylation pathways.Conclusions Aberrant ASEs exist in CLL,and the altered expression and splicing levels of SFs may contribute to this dysregulation.