# bZIP-Domain Variant Allele Frequency Helps to Refine Risk Stratification in CEBPA-Mutated AML

## TL;DR

This study shows that measuring the variant allele frequency in the bZIP domain of CEBPA mutations improves risk prediction for relapse in AML patients.

## Contribution

The study identifies bZIP-domain variant allele frequency as a more effective prognostic marker than maximum VAF in CEBPA-mutated AML.

## Key findings

- A threshold of 44.2% for bZIP-domain VAF was found to best predict relapse risk.
- High bZIP-domain VAF was associated with worse event-free survival and higher leukemia burden.
- bZIP-domain VAF outperformed maximum VAF in multiple subgroups and was confirmed as an independent risk factor.

## Abstract

Objectives: To investigate the prognostic value of CEBPA (CCAAT/enhancer-binding protein α) molecular features, such as variant allele frequency (VAF), in patients with de novo acute myeloid leukemia (AML). Methods: Next-generation sequencing (NGS) was used to detect CEBPA mutations in 162 patients with newly diagnosed AML (except acute promyelocytic leukemia). Results: We established 44.2% as the optimal threshold for both maximum VAF and bZIP-domain VAF. The high-VAF group showed higher leukemia burden and inferior event-free survival (EFS). bZIP-domain VAF demonstrated superior prognostic value over maximum VAF (HR: 3.174 vs. 2.460) and was validated across subgroups, namely cytogenetically normal acute myeloid leukemia (CN-AML), chemotherapy-only, and low/intermediate-risk subgroups. Multivariate analysis confirmed high bZIP-domain VAF and DNMT3A mutation as independent risk factors. Conclusions: Our results confirm that the bZIP-domain VAF of CEBPA mutations is a more effective predictor of relapse than the maximum VAF, offering a valuable tool for the early identification of patients at high risk of relapse.