SF3B1 mutation constrains the spectrum of drivers of clonal progression. (A) Distribution of MDS/AML diagnostic categories in the SF3B1-mutant patient cohort based on WHO 2016 classification. Mutation analysis was restricted to the highlighted low-risk (BM blasts <5%) and high-risk groups (BM blasts ≥5%). (B) Frequency of SF3B1 comutated driver genes in the SF3B1-mutant patient cohort. n, number of mutated patients. Dashed box indicates genes mutated in ≥4% of patients. Only genes mutated in ≥1% of patients are shown. (C) Odds ratio distribution of recurrent SF3B1 comutated genes vs mutational frequency in the high-risk group. Red color indicates genes with the highest odds ratio of HR disease. (D) Hazard ratio for the risk of progression to AML or death, based on univariate Cox regression analysis. Red color indicates genes with the highest hazard ratio of leukemic transformation or death. (E) Frequency distribution of VAF of SF3B1 and RUNX1 (top), and SF3B1 and STAG2 (bottom) mutations in SF3B1-mutant MDS/AML. HR, high-risk group; LFS, leukemia free survival; LR, low-risk group; MDS-del5q, MDS with isolated del(5q); MDS-EB, MDS with excess blasts; MDS-RS, MDS with ring sideroblasts; MDS-SLD/MLD, MDS with single lineage/multilineage dysplasia; MDS-U, MDS, unclassifiable; WHO, World Health Organization.