Hematology · 14 h ago
Large AML cohort maps RAS mutations and treatment-specific survival associations
A molecular profiling analysis of 8,553 patients with newly diagnosed acute myeloid leukemia found RAS mutations in 21%. Their associations with overall survival varied by mutation background and treatment intensity.
- RAS mutations occurred in 21% of 8,553 newly diagnosed AML cases.
- NRAS survival associations differed across genomic subgroups.
- RAS mutations were linked to poorer survival in selected venetoclax-treated subgroups.
Researchers analyzed centralized molecular profiling data from 8,553 patients with newly diagnosed acute myeloid leukemia (AML) to characterize RAS mutations and their clinical associations. RAS mutations were identified in 1,775 patients (21%): 1,103 had NRAS, 445 had KRAS, and 227 had both. Multiple RAS mutations occurred in 23% of patients, and mutations most often affected P-loop hotspots.
Survival associations differed by genomic background and treatment. Among intensively treated patients, NRAS mutations were associated with worse overall survival in AML with myelodysplasia-related features (HR 1.32), but better survival in patients with NPM1 (HR 0.61) or FLT3-ITD mutations (HR 0.63). KRAS mutations were associated with inferior survival (HR 1.41). In patients receiving non-intensive venetoclax-based regimens, RAS mutations were associated with markedly inferior survival in those with NPM1 (HR 2.98) or IDH1/2 mutations (HR 4.06).
The findings show that RAS status alone does not capture prognosis across AML subgroups. The observational analysis may inform risk stratification and research into RAS-targeting strategies, but the supplied abstract does not establish treatment benefit or support changes to clinical management.
In practice
For clinicians interpreting AML molecular profiles, these findings suggest that the prognostic association of RAS mutations depends on the co-mutation profile and treatment intensity: NRAS was associated with both worse and better survival across intensively treated subgroups, while RAS mutations were associated with poor survival in selected patients receiving non-intensive venetoclax-based regimens. This is observational evidence and does not show that changing treatment based on RAS status improves outcomes; it does not justify a management change on its own.
AI-generated clinical interpretation · Not editor-reviewed
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Blood: Genomic and clinical landscape of RAS mutations in acute myeloid leukemia ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.