Hematology · 1 h ago
CSF3R mutations show context-dependent prognosis in acute myeloid leukemia
A cohort study of 2,500 patients with newly diagnosed de novo AML treated with intensive induction found CSF3R mutations in 3.5%. Their prognostic associations varied by AML subtype and mutation class, with the strongest adverse outcomes in CEBPA-bZip AML.
- CSF3R mutations occurred in 3.5% of the cohort.
- Adverse outcomes were clearest in CEBPA-bZip AML.
- Mutation class influenced prognostic associations.
- Study included intensively treated patients with de novo AML.
Researchers analysed 2,500 patients with newly diagnosed de novo non-acute promyelocytic AML who received intensive induction therapy. The cohort study assessed outcomes associated with CSF3R mutations overall, by co-occurring molecular subtype, and by functional mutation class. CSF3R mutations were identified in 3.5% of patients and frequently co-occurred with CEBPA-bZip mutations and RUNX1::RUNX1T1 fusions.
Across the full cohort, CSF3R mutations were associated with inferior relapse-free survival, but not overall or event-free survival. The adverse association was most consistent in CEBPA-bZip AML: mutations were associated with worse event-free survival (hazard ratio [HR], 2.76; p=0.001) and relapse-free survival (HR, 2.66; p=0.002), with associations persisting after multivariable adjustment and time-dependent modelling of transplantation. Membrane-proximal activating mutations were associated mainly with inferior relapse-free survival in the overall cohort (HR, 2.27; p=0.001); cytoplasmic-tail truncating mutations showed no consistent adverse effect overall.
The findings suggest that CSF3R mutation status may have different prognostic significance depending on molecular context and mutation class. The study is observational and limited to intensively treated patients; the CTTM subgroup in CEBPA-bZip AML was small. The results do not establish a change in treatment or risk-classification recommendations.
In practice
In patients with newly diagnosed de novo AML receiving intensive induction, CSF3R mutation status was associated with outcomes differently across molecular contexts; the strongest adverse associations were in CEBPA-bZip AML. These findings may inform prognostic assessment, but the study is observational and does not show that treatment should change or establish a new risk-classification recommendation. The results may not apply to patients receiving other treatment approaches, and the CTTM subgroup in CEBPA-bZip AML was small.
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British Journal of Haematology: Subtype‐ and functional class‐dependent prognostic impact of CSF3R mutations in acute myeloid leukaemia: A cohort study of 2500 patients ↗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.