[Prognostic significance of CEBPA gene mutations in acute myeloid leukemia]

Objective: To investigate the prognostic value of CEBPA gene mutations in patients with newly diagnosed acute myeloid leukemia (AML) . Methods: A retrospective cohort analysis was conducted on the clinical data from 237 CEBPA-mutated AML patients who received intensive chemotherapy induction at the First Affiliated Hospital of Soochow University between January 2016 and December 2024. Clinical characteristics, treatment responses, and prognosis were compared among different mutation subgroups. Results: Among 237 patients, 182 (76.8%) harbored bZIP domain in-frame insertion/deletion mutations (bZIP(InDel)), 13 (5.5%) had bZIP domain missense mutations (bZIP(ms)), and 42 (17.7%) carried other mutation types (Other(mut)). Compared with the latter two groups, patients in the bZIP(InDel) group had a younger age at onset (P<0.001), a higher GATA2 mutation rate (P<0.001), and lower mutation rates of NPM1 and DNMT3A (both P<0.05). After two courses of induction therapy, the bZIP(InDel) group achieved significantly higher complete remission (CR) /CR with incomplete hematologic recovery (CRi) rates and measurable residual disease (MRD) -negative rates than the bZIP(ms) and Other(mut) groups (CR/CRi rates: 99.4% vs 75.0% vs 86.8%, P<0.001; MRD-negative rates: 88.6% vs 77.8% vs 66.7%, P=0.008). With a median follow-up of 41 months, the 3-year overall survival (OS) and relapse-free survival (RFS) rates in the bZIP(InDel) group were 90.7% and 72.1%, respectively. Multivariate analysis revealed that CEBPA bZIP(InDel) was an independent favorable prognostic factor for both OS (HR=0.16, 95%CI: 0.06-0.40, P<0.001) and RFS (HR=0.31, 95%CI: 0.17-0.57, P<0.001). Within the bZIP(InDel) group, patients achieving CR/CRi after one course of induction had a superior 3-year OS rate compared with those achieving CR/CRi after two courses (88.3% vs 48.9%, P=0.050). Although allogeneic hematopoietic stem cell transplantation performed during the first CR (CR1) significantly improved the 3-year RFS rate (89.7% vs 57.6%, P<0.001), this benefit did not translate into an OS advantage (P=0.376). Additionally, concurrent KIT mutations were associated with a lower 3-year OS rate (65.6% vs 91.7%, P=0.042), and concurrent CSF3R mutations were associated with a lower 3-year RFS rate (42.9% vs 75.1%, P<0.001) . Conclusion: CEBPA bZIP(InDel) confer a distinct prognostic value. Patients in this subgroup derive substantial benefit from chemotherapy; however, the presence of concurrent KIT or CSF3R mutations is frequently associated with unfavorable outcomes.