Characteristics and clinical outcomes of patients with myeloid malignancies and cohesin mutations

The prognostic impact of cohesin mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is controversial. In patients with AML and MDS who underwent next-generation sequencing at the authors' center during 2017-2023, the authors assessed the landscape of cohesin mutations and the impact of co-occurring mutations on overall survival (OS) and compared outcomes between patients with cohesin mutations and those with wild-type (WT) cohesin genes. The study included 83 patients, 36 with cohesin mutations (STAG2, n = 28; SMC1A, n = 7; SMC3, n = 3; co-expression of cohesin mutations, n = 2) and 47 with WT cohesin genes. Of the 36 patients with cohesin mutations, 17 (47%) had AML (six de novo and 11 secondary), and 19 (53%) had MDS. Patients who had STAG2 mutations had better median OS than patients who had only SMC1A and SMC3 mutations (26 vs. 10 months; p = .043). SRSF2 mutation was the most frequent co-occurring mutation (n = 12; 33%) and was associated with worse median OS than WT SRSF2 (13 vs. 43 months; p = .016). Seven patients (19%) with cohesin mutations underwent hematopoietic transplantation; their median OS was 70 months. Compared with the WT cohesin group, patients who had cohesin mutations were more likely to have adverse-risk AML (82% vs. 53%). The median OS was similar among patients with adverse-risk AML in the cohesin-mutation and WT cohesin groups (10 vs. 14 months, respectively; p = .9). The current study provides insight into the prognostic impact of cohesin mutations and co-occurring mutations in patients with myeloid malignancies.