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

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 (SF3B1^mut ; 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 SF3B1^mut was significantly longer compared to t-MDS SF3B1^mut but not significantly different when adjusted for comorbidities. Comparing t-MDS wild-type SF3B1 (SF3B1^WT ; n = 241) to t-MDS SF3B1^mut (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 SF3B1^WT versus SF3B1^mut . When applying the International Working Group for Prognosis of MDS (IWG-PM) proposed SF3B1 criteria, OS was significantly shorter in SF3B1^mut t-MDS compared to de novo MDS SF3B1^mut with no significance in AML transformation. Survival was compared between t-MDS SF3B1^mut who met the new proposed IWG-PM criteria to t-MDS SF3B1^mut who did not meet criteria to survival of SF3B1^WT 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.