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December 8, 2025BloodOpen Access

Identifying novel 'druggable’ targets via Npm1A-turboid fusion and mass spectrometry to overcome genetic or adaptive resistance to menin inhibitors in mtNPM1 AML

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Authors

CMChristopher P. MillCWClaes WahlestedtNDNaval Daver

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Overview

Analysis identifies eIF4A as a target in mtNPM1 AML, suggesting new treatment strategies for resistant cells.

Key Points

  • eIF4A targeting reduced cell viability in mtNPM1 AML, indicating therapeutic promise against resistance.
  • Mass spectrometry revealed novel interactors, including eIF4A, highlighting potential druggable targets in AML.
  • CRISPR/Cas9 was used to create models for studying mi-resistant mtNPM1 in AML cells with various treatments.
  • Results imply that targeting eIF4A could effectively synergize with existing therapies in resistant AML models.

Cite This Study

Mill et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dcefhttps://doi.org/10.1182/blood-2025-1500
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Also Consider

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

  1. 1Preclinical activity of investigational menin inhibitor DSP-5336 (Enzomenib)-based combinations against MLL1-rearranged (MLL-r) or mutant-NPM1 AML models2025 · 1 citations
  2. 2Protein degradation of MYC/GSPT1 combined with menin inhibition overcomes resistance to menin inhibition in KMT2A-rearranged Acute Myeloid Leukemia2025 · 1 citations
  3. 3Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review2025 · 7 citations
  4. 4Menin inhibitors for NPM1-mutated and KMT2A-rearranged relapsed/refractory acute myeloid leukemia (AML): A systematic review and meta-analysis2025
  5. 5Menin-inhibition boosts CAR-T cell therapy against NPM1 mutated and KMT2A-rearranged acute myeloid leukemia2025 · 1 citations