Prevalence and prognostic significance of c-KIT mutations in core binding factor acute myeloid leukemia: A comprehensive large-scale study from a single Chinese center

To clarify the prevalence and prognostic significance of c-KIT mutations in patients with core binding factor acute myeloid leukemia (CBF-AML), a total of 351 patients who were categorized as pediatric t(8;21), adult t(8;21), pediatric inv(16), or adult inv(16) were screened at diagnosis for c-KIT mutations in exons 17 and 8 using direct sequencing. A total of 250 patients underwent follow-up. Overall, 36.5% of the patients had a c-KIT mutation. Adult t(8;21) and inv(16) patients had mutations predominantly in exons 17 and 8, respectively. Higher White blood cell (WBC) count, WBC index, and AML1-ETO transcript levels in adult t(8;21) patients were significantly associated with c-KIT mutations and mutations in exon 17 (P ≤ 0.030). c-KIT mutations in adult t(8;21) patients were significantly correlated with a high cumulative incidence of relapse (CIR, P = 0.0070) at 2 years and a low 2-year disease-free survival (DFS, P = 0.013) and overall survival (OS, P = 0.0055). However, no significant difference was revealed in the effect of c-KIT mutations on outcome of adult inv(16) and pediatric t(8;21) patients (all P > 0.05). Multivariate analysis revealed that c-KIT mutation is an independent prognostic factor for relapse, DFS, and OS (P ≤ 0.016) in adult t(8;21) AML patients. Therefore, with regard to c-KIT mutation, CBF-AML is a heterogeneous disease. c-KIT mutations have a strong adverse effect on the relapse and survival of adult t(8;21) AML patients.