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December 8, 2025Blood

Disrupting the PA2G4-NPM1 axis induces nucleolar stress in NPM1c AML

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Authors

RPRosa Maria Poldi Allay PatarinoBLBruno LorussoKKKun Karnchanapandh

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Overview

Experimental findings demonstrate that WS6 reduces NPM1c AML cell proliferation, suggesting potential for new treatments.

Key Points

  • This research aims to investigate the role of PA2G4 in NPM1-mutated acute myeloid leukemia and its therapeutic implications.
  • Used WS6 to inhibit PA2G4 in AML cell lines and patient-derived xenograft models.
  • Conducted co-immunoprecipitation and mass spectrometry to identify protein interactions.
  • Analyzed gene expression changes post-treatment using quantitative PCR and RNA sequencing.
  • WS6 treatment resulted in an IC50 from 0.008 to 1.8 μM in NPM1c models, inducing apoptosis.
  • Significant upregulation of 1079 genes and downregulation of 1264 genes related to nucleolar stress after WS6 treatment.
  • Flow cytometry showed reduced human CD45⁺ cells in mouse bone marrow after WS6 treatment.

Cite This Study

Patarino et al. (2025) studied this question.

synapsesocial.com/papers/69362f484fa91c937236d662https://doi.org/10.1182/blood-2025-4324
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Also Consider

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

  1. 1Targeting CCL3+mono like LSC overcomes chemotherapy resistance in NPM1 mutant AML2025
  2. 2A Comprehensive Genomic Analysis of Nucleophosmin (NPM1) in Acute Myeloid Leukemia2025 · 2 citations
  3. 3TTLL4 glutamyltransferase is a therapeutic target for NPM1-mutated Acute Myeloid Leukemia2025
  4. 4Mutant NPM1 in Acute Myeloid Leukemia Initiation and Maintenance2026
  5. 5Wildtype NUP98 cooperates with NPM1c to drive oncogenic transcription2025 · 2 citations