TY - JOUR
T1 - Prognostic impact of ASXL1 mutations in chronic phase chronic myeloid leukemia
AU - Bidikian, Aram
AU - Kantarjian, Hagop
AU - Jabbour, Elias
AU - Short, Nicholas J.
AU - Patel, Keyur
AU - Ravandi, Farhad
AU - Sasaki, Koji
AU - Issa, Ghayas C.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
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U2 - 10.1038/s41408-022-00742-1
DO - 10.1038/s41408-022-00742-1
M3 - Article
C2 - 36307398
AN - SCOPUS:85140891709
SN - 2044-5385
VL - 12
JO - Blood cancer journal
JF - Blood cancer journal
IS - 10
M1 - 144
ER -