Cohort study reveals distinct genetic profiles and prognostic outcomes between sexes in acute myeloid leukemia, highlighting the need for sex-stratified disease risk assessments.
Key Points
To comprehensively evaluate sex-specific differences in the frequency, co-occurrence, and prognostic significance of recurrent genetic alterations in adults with acute myeloid leukemia.
Analyzed mutational profiles, cytogenetics, and clinical outcomes in 1,726 adults (749 females, 977 males) treated on frontline Alliance for Clinical Trials in Oncology protocols.
Validated genetic and outcome associations in an independent cohort of 954 adults (465 females, 489 males) treated on German AML Cooperative Group frontline protocols.
Women more frequently had normal karyotypes and FLT3-ITD, DNMT3A, NPM1, or WT1 mutations, whereas men more often presented with complex karyotypes and ASXL1, SRSF2, U2AF1, RUNX1, or KIT mutations.
Women were enriched in the 2022 European LeukemiaNet intermediate-risk category, while men were predominantly classified into the adverse-risk category.
SF3B1 mutations were identified as male-specific adverse outcome prognosticators in patients under 60 years of age, accompanied by sex-divergent gene-expression and alternative splicing profiles.