Validation of the Clinical Significance of CEBPA bZIP Mutations in Acute Myeloid Leukemia.
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BACKGROUND: The study aimed to investigate the characteristics of CEBPA mutations in Chinese acute myeloid leukemia (AML) patients. METHODS: We retrospectively analyzed the clinical features and prognostic implications in 358 AML patients, except acute promyelocytic leukemia (APL). Mutations were detected by Sanger sequencing or next-generation sequencing. RESULTS: A total of 57 mutations were detected in 47 (13.1%) out of 358 patients. Among 47 CEBPA mutated (CEBPAmut) patients, 18 (38.3%) had in-frame mutation in bZIP domain (bZIPinf), and the remaining 29 had frameshift or missense mutation in or out of bZIP domain (bZIPother). Compared with CEBPA wild-type (CEBPAwt) patients, the bZIPinf group was younger and was predominantly distributed in AML without or with differentiation (both p < 0.05). bZIPinf group had a significantly higher complete remission (CR) rate after two courses of induction therapy than the CEBPAwt group (84.6% vs. 56.1%, p = 0.044), whereas bZIPother group had a CR rate of 41.7% (p = 0.025). The median overall survival (OS) of bZIPinf patients was significantly better than that of CEBPAwt (p = 0.014). Multifactorial Cox regression analysis showed that bZIPinf mutation was an independent predictor of favorable prognosis in AML patients (p = 0.024; HR = 0.356; 95% CI: 0.145 - 0.873). CONCLUSIONS: In summary, our data confirm that CEBPA bZIPinf mutation is an independent factor of favorable prognosis in AML patients.