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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

Targeting PA2G4 leads to significant sensitivity reduction in acute myeloid leukemia cells, indicating a novel therapeutic approach.

Key Points

  • Disruption of the PA2G4-NPM1 complex induces nucleolar stress, affecting acute myeloid leukemia proliferation.
  • IC50 for WS6 in NPM1-mutation carrying samples ranged from 0.008 to 1.8 μM, showing significant sensitivity.
  • The approach involved analyzing the RNA-binding protein PA2G4 and its interactions within NPM1c models.
  • Potential therapeutic significance lies in revealing the role of PA2G4 in regulating gene expression related to ribosome biogenesis.

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. 4Wildtype NUP98 cooperates with NPM1c to drive oncogenic transcription2025 · 2 citations
  5. 5Proteogenomic analysis of NPM1-mutated AML reveals clinical heterogeneity related to differentiation states and mitochondrial metabolism2025