Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia

Background The epigenetic regulator additional sex combs-like 1 ( ASXL1 ) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1 -mutated ( ASXL1 +) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1 + AML. Methods We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1 + AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Results In a total of 91 ASXL1 + AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 10 9 /L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1 + AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1 + AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1 + AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1 + AML. The median OS was not attained in single-hit ASXL1 + AML, 29.53 months in double-hit ASXL1 + AML, and 6.67 months in triple-hit ASXL1 + AML ( P = 0.003). The median EFS was not attained in single-hit ASXL1 + AML, 29.53 months in double-hit ASXL1 + AML, and 5.47 months in triple-hit ASXL1 + AML ( P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1 + AML patients. Conclusions Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1 + AML patients. Our primary data suggest that the risk factors in ASXL1 + AML contribute to the poor outcome of these patients. The management of ASXL1 + AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation.