Prognostic value of CEBPA bZIP signatures in cytogenetically normal acute myeloid leukaemia.
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Recent studies revealed that CEBPA with basic leucine zipper (bZIP) in-frame mutation (CEBPAbZIP-inf) is the bona fide entity with a favourable prognosis in acute myeloid leukaemia. However, the mechanism by which the bZIP signatures influence risk stratification remains unclear. We identified 141 patients with CEBPAbZIP-inf. Variant allele fraction (VAF) (cumulative incidence of relapse [CIR], VAFhigh vs. VAFlow, 74.0% vs. 27.0%, p < 0.001) and base change (≤ vs. >3 bases, 39.1% vs. 60.6%, p = 0.042) of bZIP mutations were associated with CIR. These two factors, along with the white blood cell count and measurable residual disease after first consolidation, could stratify patients into three risk subgroups (CIR, low vs. medium vs. high risk, 15.2% vs. 47.1% vs. 83.0%, p < 0.001). Compared with no transplantation, receiving a transplantation significantly decreased the relapse rates in medium-risk (transplantation vs. no transplantation, 11.6% vs. 49.7%, p = 0.009) and high-risk patients (5.6% vs. 84.1%, p < 0.001) but not low-risk (0% vs. 15.2%, p = 0.220). However, only high-risk patients could benefit from transplantation in terms of overall survival (100% vs. 59.7%, p = 0.003). Our study revealed the heterogeneity of CEBPAbZIP-inf patients and suggested a risk-adapted treatment modality. Transplantation is recommended for high-risk patients and consolidation chemotherapy is recommended for low-risk and medium-risk patients.