Molecular characterization of AML-MRC reveals TP53 mutation as an adverse prognostic factor irrespective of MRC-defining criteria, TP53 allelic state, or TP53 variant allele frequency.

ABSTRACT:

Background

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) generally confers poor prognosis, however, patient outcomes are heterogeneous. The impact of TP53 allelic state and variant allele frequency (VAF) in AML-MRC remains poorly defined.

Methods

We retrospectively evaluated 266 AML-MRC patients who had NGS testing at our institution from 2014 to 2020 and analyzed their clinical outcomes based on clinicopathological features.

Results

TP53 mutations were associated with cytogenetic abnormalities in 5q, 7q, 17p, and complex karyotype. Prognostic evaluation of TP53^MUT AML-MRC revealed no difference in outcome between TP53 double/multi-hit state and single-hit state. Patients with high TP53^MUT variant allele frequency (VAF) had inferior outcomes compared to patients with low TP53^MUT VAF. When compared to TP53^WT patients, TP53^MUT patients had inferior outcomes regardless of MRC-defining criteria, TP53 allelic state, or VAF. TP53 mutations and elevated serum LDH were independent predictors for inferior OS and EFS, while PHF6 mutations and transplantation were independent predictors for favorable OS and EFS. NRAS mutation was an independent predictor for favorable EFS.

Conclusions

Our study suggests that TP53^MUT AML-MRC defines a very-high-risk subentity of AML in which novel therapies should be explored.

SUBMITTER: Zhao D 

PROVIDER: S-EPMC10067127 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature