Molecular abnormalities are frequent in core-binding factor (CBF) AMLs, but their prognostic relevance is controversial. Sixty-two patients were retrospectively analyzed and 47 harbored at least one gene mutation with a next-generation-sequencing assay. The most common molecular mutation was KIT mutation (30.6%), followed by NRAS (24.2%) and ASXL1 (14.5%) mutations, which was associated with a higher number of bone marrow blasts (p =.049) and older age (p =.027). The survival analysis showed KIT mutation adversely affected the overall survival (OS) (p =.046). NRAS mutation was associated with inferior OS (p =.016) and RFS (p =.039). Eight patients carried co-mutations of KIT and NRAS and had worse OS (p =.012) and RFS (p =.034). The multivariate analysis showed age ≥60 years and additional chromosomal abnormalities were significant adverse factors for OS. Thus, co-mutations of KIT and NRAS were significantly associated with a poor prognosis and should be taken into account when assessing for prognostic stratification in patients with CBF-AML. [ABSTRACT FROM AUTHOR]