Prognostic impact of ASXL1 mutations in chronic phase chronic myeloid leukemia

While the clinical impact of mutations in the ABL1 gene on response to therapy in chronic phase chronic myeloid leukemia (CP-CML) is well established, less is known about how other mutations affect prognosis. In a retrospective analysis, we identified 115 patients with CML (71 chronic, 15 accelerated and 29 blast phase) where targeted next-generation sequencing of genes recurrently mutated in myeloid leukemias was performed. ASXL1 was the most frequently mutated gene in the chronic (14%) and accelerated phase (40%) CML patients, whereas RUNX1 (20%) was the most common mutation in blast phase. Compared with wild-type ASXL1, CP-CML with mutant ASXL1 was associated with worse event-free survival (EFS) (median of 32.8 vs 88.3 months; P = 0.002) and failure-free survival (median of 13.8 vs 57.8 months; P = 0.04). In a multivariate analysis, ASXL1 mutation was the only independent risk factor associated with worse EFS in chronic phase CML with a hazard ratio of 4.25 (95% CI 1.59–11.35, P = 0.004). In conclusion, mutations in ASXL1 are associated with worse outcomes when detected in chronic phase CML.