Genomic and clinical landscape of RAS mutations in acute myeloid leukemia.

21% of newly diagnosed AML patients harbor RAS mutations, with NRAS mutations showing higher prevalence of Q61 hotspots and multiple RAS mutations occurring in 23%.

• Why it matters: Understanding the genomic and clinical landscape of RAS mutations in AML is crucial for improving risk stratification and developing targeted therapies, as their prognostic impact varies with genetic background and treatment.
• What they did: Analyzing molecular data from 8,553 AML patients, the study characterized mutation hotspots, associations with other pathway mutations, and evaluated the prognostic significance of RAS mutations under different treatment regimens.
• The result: KRAS mutations predicted worse overall survival, and RAS mutations in NPM1 or IDH1/2 mutated patients under venetoclax-based therapy were linked to markedly inferior outcomes, informing future risk assessment and targeted strategies.