CCAAT/enhancer-binding protein alpha basic leucine zipper in-frame insertion/deletion (CEBPA bZIP-InDel-inf) defines...

This study investigated how cytosine-cytosine-adenine-adenine-thymine (CCAAT)/enhancer-binding protein alpha (CEBPA) mutation sites and types affect the prognosis of acute myeloid leukaemia (AML). It specifically analysed the clinical and genetic features of AML patients harbouring CEBPA basic leucine zipper in-frame insertion/deletion (CEBPA bZIP-InDel-inf) mutations and identified prognostic factors in this subtype. Prognostic factors in CEBPA bZIP-InDel-inf subgroup were examined in depth. Overall survival (OS) and relapse-free survival (RFS) censoring models were built, informative censoring was adjusted using inverse probability of censoring weighting, and stabilized weights were applied in weighted Cox regression analyses. Risk scores for OS and RFS were then developed from multivariable results. Ninety-three patients with CEBPA mutation, 56 had CEBPA bZIP-InDel-inf. Compared with CEBPA bZIP-InDel-inf, CEBPA non-InDel had a worse prognosis. Within the bZIP region, bZIP-InDel-inf also showed better outcomes than other mutation types, especially in double-mutated cases. In weighted multivariate analysis, higher white blood cell count, blast cell count and M4/M5 phenotype independently predicted worse OS, while higher variant allele frequency (VAF), colony stimulating factor 3 receptor (CSF3R) mutation and lower haemoglobin predicted worse RFS. These variables enabled clear OS and RFS risk stratification. CEBPA bZIP-InDel-inf is a favourable CEBPA-mutated AML subtype. Further research is needed to elucidate the role of bZIP-domain-mutated proteins.