Impact of different CEBPA mutations on therapeutic outcome in acute myeloid leukemia

Biallelic mutations of the CEBPA gene (CEBPA^bi) are generally associated with favorable prognosis in patients with acute myeloid leukemia (AML). Monoallelic mutations of the CEBPA gene in carboxy-terminal DNA-binding region (CEBPA^smbZIP) and amino-terminal transactivation domains (CEBPA^smTAD) indicate distinct clinical characteristics and therapeutic outcomes. However, further investigation is required to fully understand these differences. In this retrospective study, we enrolled 77 AML patients with CEBPA mutations, including 53 with CEBPA^bi, 12 with CEBPA^smbZIP and 12 with CEBPA^smTAD. The clinical characteristics of the three CEBPA^mut groups presented significant differences in age, FAB classification, hemoglobin level and platelet count at diagnosis. The CEBPA^smTAD group exhibited shorter 2-year overall survival (OS) and relapse-free survival (RFS) compared to the CEBPA^bi group and CEBPA^smbZIP group in AML patients. The most common co-mutations observed in CEBPA^mut AML patients were TET2 and GATA2, which had no effect on prognosis. 2-year RFS of 27 CEBPA^mut AML patients who underwent allo-HSCT was better than those who did not. MRD3 positive was identified as an influencing factor for 2-year OS and RFS. Allo-HSCT was found to improve the prognosis of CEPBA^mut AML patients with positive MRD3 and adverse co-mutations.