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December 8, 2025BloodOpen Access

Functional classification of monoallelic TP53 mutations refines prognostic stratification in myelodysplastic neoplasms

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Authors

EAEva AltrockWHWolf‐Karsten Hofmann

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Overview

This research finds that dominant-negative TP53 mutations worsen outcomes in myelodysplastic disorders, suggesting integrated risk models.

Key Points

  • The aim was to explore the prognostic significance of monoallelic TP53 mutations in myelodysplastic neoplasms (MDS).
  • Survival data analyzed from IWG and J-MDS cohorts with over 4,500 MDS patients.
  • TP53 variants categorized based on loss of function and dominant-negative effects.
  • Phenotypic score developed to assess the functional impact of TP53 mutations.
  • Patients with monoallelic TP53 mutations and high phenotypic scores had significantly worse overall survival compared to those with lower scores.
  • Median overall survival was 13.8 months for high phenotypic score patients versus 39.2 months for low score patients.
  • Differences in allele frequency did not majorly influence outcomes, impacting both low- and high-risk MDS patients.

Cite This Study

Altrock et al. (2025) studied this question.

synapsesocial.com/papers/69362f4e4fa91c937236d825https://doi.org/10.1182/blood-2025-3835
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Effect of Biallelic TP53 Mutations in Changing the Subclassification of Myelodysplastic Neoplasm2024
  2. 2Prognostic impact of TP53 mutation status and variant allele frequency in myelodysplastic syndromes: A meta-analysis of prognosis and transplant outcomes2025 · 1 citations
  3. 3Comparative outcome and prognostic factor analysis among MDS/AML patients with TP53 mutations, snps, and wild type2025 · 4 citations
  4. 4Clinical implications of TP53 mutations (TP53MT) in patients (pts) with higher risk Myelodysplastic Syndromes (HR-MDS) treated with hypomethylating agents (HMA) and allogeneic hematopoietic transplantation (allo-HCT): An analysis from the international consortium of MDS (icMDS) validate database2025
  5. 5Characteristics and prognostic implications of <i>TP53</i> mutations in Chinese patients with myelodysplastic syndromes2025 · 3 citations