Faculty, Staff and Student Publications

Language

English

Publication Date

10-17-2024

Journal

Blood

DOI

10.1182/blood.2024023840

PMID

39074355

Abstract

Mutations in the TP53 gene, particularly multihit alterations, have been associated with unfavorable clinical features and prognosis in patients diagnosed with myelodysplastic syndrome (MDS). Despite this, the role of TP53 gene aberrations in MDS with isolated deletion of chromosome 5 [MDS-del(5q)] remains unclear. This study aimed to assess the impact of TP53 gene mutations and their allelic state in patients with MDS-del(5q). To that end, a comprehensive analysis of TP53 abnormalities, examining both TP53 mutations and allelic imbalances, in 682 patients diagnosed with MDS-del(5q) was conducted. Twenty-four percent of TP53-mutated patients exhibited multihit alterations, whereas the remaining patients displayed monoallelic mutations. TP53-multihit alterations were predictive of an increased risk of leukemic transformation. The impact of monoallelic alterations was dependent on the variant allele frequency (VAF); patients with TP53-monoallelic mutations and VAF < 20% exhibited behavior similar to TP53 wild type, and those with TP53-monoallelic mutations and VAF ≥20% presented outcomes equivalent to TP53-multihit patients. This study underscores the importance of considering TP53 allelic state and VAF in the risk stratification and treatment decision-making process for patients with MDS-del(5q).

Keywords

Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Young Adult, Alleles, Chromosome Deletion, Chromosomes, Human, Pair 5, Gene Frequency, Mutation, Myelodysplastic Syndromes, Prognosis, Tumor Suppressor Protein p53

Published Open-Access

yes

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