Clinicopathologic features of SF3B1^K666N MDS. (A) The distribution of publicly available mutations in exons 14 and 15 of SF3B1 for MDS-RS, MDS-EB, and AML show enrichment of SF3B1^K666N with increasing disease severity. Notably, E622D is absent in MDS-EB and AML, in contrast to MDS-RS. (B) In our cohorts, compared with patients with other SF3B1 mutations, SF3B1^K666N patients exhibited higher IPSS-R scores. (C) SF3B1^K666N patients had similar white blood cells counts (WBC; left panel), slightly higher hemoglobin levels (Hb; center panel), and lower platelets (PLTs; right panel). (D) SF3B1^K666N patients had decreased RSs. (E) Among all SF3B1^MUT patients, survival was shorter in those with SF3B1^K666N (left panel). Survival was equally poor in both groups with higher IPSS-R MDS (middle panel), but lower IPSS-R SF3B1^K666N patients had shorter survival (right panel). Univariate (Mantel-Cox) and multivariate (Cox regression including IPSS-R categories) P values are shown. *P < .05, ****P < .0001, 2-tailed Student t test. ***P < .001, χ² test.