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December 8, 2025Blood

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

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Authors

NCNathalie CerveraCentre National de la Recherche ScientifiqueCCChong Chyn ChuaThe University of MelbourneSGSylvain GarciazCentre National de la Recherche Scientifique

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Overview

Single-cell analysis reveals multi-hit TP53 mutations in AML, suggesting challenges in venetoclax therapy.

Key Points

  • To characterize the clonal dynamics and lineage associations of TP53 mutated AML using single-cell sequencing.
  • Analyzed 17 bone marrow samples from 9 patients with TP53m AML using single-cell DNA and protein sequencing.
  • Utilized next-generation sequencing and tested for multi-hit TP53 abnormalities.
  • Performed enrichment of CD34/117+ cells for a more detailed analysis.
  • Identified multi-hit TP53 abnormalities mainly in AML blasts, often showing loss of heterozygosity.
  • Found a minor ancestral TP53 heterozygous population in the blast compartment.
  • Detected selective expansion of TP53m multi-hit clones in patients undergoing 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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