What does this research mean for the field?

In Asian patients with myelodysplastic neoplasms, TP53 variant allele frequency and the presence of multiple TP53 mutations strongly correlate with increased disease severity and worse prognostic risk classifications. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to examine the mutation landscape and clinical features associated with TP53-mutated myelodysplastic neoplasms in a Chinese population.

May 31, 2026Open Access

Genetic and Clinical Features in TP53 ‐Mutated Patients With Myelodysplastic Neoplasms: A Retrospective Study Based on Next‐Generation Sequencing Data

Key Points

This research aims to examine the mutation landscape and clinical features associated with TP53-mutated myelodysplastic neoplasms in a Chinese population.
Analyzed 161 TP53-mutated patients from 1589 newly diagnosed MDS using next-generation sequencing data.
Used a targeted 96-gene sequencing panel to identify genomic alterations.
Examined the correlation between TP53 variant allele frequency and clinical parameters such as hemoglobin levels and risk classifications.
76.9% of mutations were missense, with frequent co-occurrence of mutations in DNMT3A, TET2, and ASXL1.
Strong correlation between TP53 variant allele frequency and disease severity parameters (all p < 0.05).
Patients with multiple TP53 mutations had worse risk classifications compared to those with a single mutation.

Abstract

ABSTRACT Background The recent fifth edition of World Health Organization and International Consensus Classification in 2022 recognized TP53 ‐mutated myelodysplastic neoplasms (MDS) as a distinct entity requiring multi‐hit classification. Literatures indicate that TP53 variant alle frequency (VAF) correlates with clinical outcomes. However, comprehensive studies that characterize the full mutation landscape and clinical correlations in Asian populations are still limited. Aims This research aims to elucidate the mutation spectrum and baseline characteristics of TP53 ‐mutated MDS in a Chinese cohort, thereby enhancing clinical understanding and treatment approaches. Methods and Results A total of 161 TP53 ‐mutated patients from 1589 newly diagnosed MDS with next‐generation sequencing (NGS) data via a targeted 96‐gene sequencing panel were analyzed to assess genomic alterations. Among 161 TP53 ‐mutated patients (10.1% of 1589 MDS cases), we identified a predominance of missense mutations (76.9%) and frequent co‐occurrence with epigenetic modifiers, notably DNMT3A (11.8%), TET2 (10.6%), and ASXL1 (9.3%). Critically, TP53 VAF correlated strongly with disease severity parameters, including hemoglobin levels, blast percentage, karyotype, and International Prognostic Scoring System (IPSS), revised IPSS (IPSS‐R) risk and IPSS‐Molecular (IPSS‐M) classifications (all p < 0.05), suggesting that TP53 VAF serves as an important biomarker for risk stratification. In addition, patients with multiple TP53 mutations harbored significantly worse IPSS, IPSS‐R, and IPSS‐M risk classifications compared to those with a single TP53 mutation. Conclusions This study underscores the importance of TP53 mutations in Asian MDS patients, contributing to genetic profiling in risk stratification and therapeutic decision‐making.

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