Low-VAF TP53-Mutated AML Displays Distinct Biological Features in a Single-Center Cohort

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• The International Consensus Classification (ICC) uses a 10% variant allele frequency (VAF) threshold for TP53-mutated acute myeloid leukemia (AML).
• The optimal VAF cutoff for defining oncogenic TP53 mutations in AML is uncertain.
• Biological and clinical features of TP53-mutated AML with low VAF (<10%) are not well-characterized.

Purpose of the Study:

• To investigate the clinical and biological characteristics of TP53-mutated AML stratified by a 10% VAF cutoff.
• To compare outcomes between TP53-mutated AML with VAF < 10% and VAF ≥ 10%.

Main Methods:

• Single-center retrospective cohort study.
• Stratification of TP53-mutated AML patients based on a 10% VAF cutoff.
• Comparison of clinical, cytogenetic, molecular, and survival data between groups.

Main Results:

• The VAF < 10% group showed fewer adverse cytogenetic abnormalities but a more adverse molecular profile (EVI1 overexpression, higher co-mutation burden, ASXL1/SRSF2 mutations).
• TP53 hotspot mutations were more frequent in the low VAF group.
• Both groups had a poor prognosis; the low VAF group had numerically longer survival, but without statistical significance.

Conclusions:

• The ICC 10% VAF threshold appears clinically relevant for TP53-mutated AML.
• TP53-mutated AML with VAF < 10% may represent a distinct biological subgroup.
• Further multicenter studies are needed to validate the VAF threshold for prognostic evaluation and treatment individualization.