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

Area of Science:

• Hematology
• Molecular Biology
• Oncology

Background:

• CCAAT/enhancer-binding protein α (CEBPA) mutations are common in acute myeloid leukemia (AML).
• The prognostic significance of CEBPA variant allele frequency (VAF) requires further investigation.

Purpose of the Study:

• To evaluate the prognostic value of CEBPA molecular features, specifically VAF, in de novo AML patients.
• To determine if bZIP-domain VAF is a better predictor of relapse than maximum VAF.

Main Methods:

• Next-generation sequencing (NGS) was employed to analyze CEBPA mutations in 162 newly diagnosed AML patients.
• Optimal VAF thresholds were established, and prognostic values were assessed using event-free survival (EFS) and multivariate analysis.

Main Results:

• An optimal threshold of 44.2% was identified for both maximum and bZIP-domain VAF.
• High VAF correlated with increased leukemia burden and inferior EFS.
• bZIP-domain VAF (HR: 3.174) showed superior prognostic value compared to maximum VAF (HR: 2.460) and was validated across subgroups.

Conclusions:

• CEBPA bZIP-domain VAF is a more potent predictor of relapse in AML than maximum VAF.
• This finding provides a valuable tool for early identification of high-risk AML patients.
• High bZIP-domain VAF and DNMT3A mutation are independent risk factors for AML.