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December 8, 2025Blood

TP53-mutated Acute Myeloid Leukemia through a single-cell lens

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Authors

NCNathalie CerveraCCChong Chyn ChuaSGSylvain Garciaz

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Overview

Analysis reveals multi-hit TP53 variants in acute myeloid leukemia, indicating challenges in therapy response with venetoclax.

Key Points

  • Multi-hit TP53 variants were predominantly observed in AML blasts, highlighting their potential role in treatment challenges.
  • Next-generation sequencing identified complex copy number changes primarily associated with TP53 multi-hit abnormalities in CD34+/117+ blasts.
  • Assessment using single-cell protein sequencing revealed that venetoclax therapy led to the expansion of dominant TP53 multi-hit clones.
  • The study points to the role of mutant IDH1 variants in potentially sensitizing TP53 multi-hit populations to venetoclax therapy.

Cite This Study

Cervera et al. (2025) studied this question.

synapsesocial.com/papers/69362f3a4fa91c937236d3d4https://doi.org/10.1182/blood-2025-5266
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Also Consider

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

  1. 1TP53-mutated AML and treatment outcomes in the era of hypomethylating agent/venetoclax therapy2025
  2. 2Decoding the molecular drivers of <i>TP53</i> ‐mutant acute myeloid leukaemia: Clinical implications and prognostic insights2025
  3. 3Targeting DNA repair vulnerabilities to eradicate TP53 mutated AML.2025
  4. 4Integrating single-cell whole genome and transcriptome sequencing to track the clonal evolution of TP53-mutated myeloid neoplasms2025
  5. 5Biallelic TP53 aberrations and double TP53 mutations are prevalent in AML/MDS patients with del(5q) complex karyotype - an NCI myelomatch and SWOG report2025 · 2 citations