Splicing factor 3B subunit 1 (SF3B1) mutation in the context of therapy-related myelodysplastic syndromes.

Abstract

Splicing factor 3B subunit 1 (SF3B1) somatic mutation in the context of therapy-related myelodysplastic syndromes (t-MDS) has not been well defined. In a large cohort of patients with MDS, those with known SF3B1 somatic mutation were compared as de novo MDS (n=289) and t-MDS with mutant SF3B1 (SF3B1mut ; n=31). Baseline characteristics, concomitant mutations, and acute myeloid leukaemia (AML) transformation were similar between the two groups. The median overall survival (OS) of de novo MDS SF3B1mut was significantly longer compared to t-MDS SF3B1mut but not significantly different when adjusted for comorbidities. Comparing t-MDS wild-type SF3B1 (SF3B1WT ; n=241) to t-MDS SF3B1mut (n=31), complex cytogenetics were seen in 37.4% versus 10.3% (p=0.009), tumour protein p53 (TP53) mutation was 36.1% versus 10% (p=0.004), and AML transformation was 34.4% compared to 12.9% (p=0.016) respectively. OS was significantly shorter in SF3B1WT versus SF3B1mut . When applying the International Working Group for Prognosis of MDS (IWG-PM) proposed SF3B1 criteria, OS was significantly shorter in SF3B1mut t-MDS compared to de novo MDS SF3B1mut with no significance in AML transformation. Survival was compared between t-MDS SF3B1mut who met the new proposed IWG-PM criteria to t-MDS SF3B1mut who did not meet criteria to survival of SF3B1WT t-MDS. OS was 53 versus 22 and 18 months respectively (p=0.006). AML transformation was 0%, 26.7% and 32.3% (p=0.021). Leukaemia-free survival was not reached among the three.