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December 8, 2025BloodOpen Access

Therapeutic effect of menin inhibitors is reversible in AML treatment and could be enhanced by the targeting of differentiation associated chromatin complex

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Authors

JMJohn MosiorJWJin Wang

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Overview

Experimental findings reveal menin inhibitors promote differentiation in AML, indicating potential for enhanced treatment strategies.

Key Points

  • This research aims to understand the long-term effects and reversibility of menin inhibitors in AML treatment.
  • Examined effects of menin inhibitors on MLL-r and NPM1c AML cell lines and primary cells for long-term treatment.
  • Assessed cell viability and growth post-inhibitor withdrawal to observe reversibility.
  • Conducted CRISPR screens targeting chromatin regulators to enhance differentiation induced by menin inhibitors.
  • Menin inhibitors led to reversible differentiation, with no significant resistance in regrown cells.
  • CD11bhi cells exhibited slower growth initially but ultimately lost differentiation markers after withdrawal.
  • Combination of MBD2 and menin inhibitors improved differentiation stability and induced cell death.

Cite This Study

Mosior et al. (2025) studied this question.

synapsesocial.com/papers/69362f444fa91c937236d602https://doi.org/10.1182/blood-2025-3295
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Also Consider

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

  1. 1Synergistic targeting of KMT2A-rearranged AML with combined LSD1 and menin inhibitors2025
  2. 2Post allo-HCT menin-inhibition enhances graft-versus-leukemia effects by endogenous retrovirus induction in AML and T-cell activation2025
  3. 3Targeting the Menin– <scp>KMT2A</scp> Axis in Acute Leukemia: From Epigenetic Dependency to Clinical Translation2026 · 1 citations
  4. 4Menin inhibition as a new therapeutic option for the myeloproliferative neoplasms2025
  5. 5Protein degradation of MYC/GSPT1 combined with menin inhibition overcomes resistance to menin inhibition in KMT2A-rearranged Acute Myeloid Leukemia2025 · 1 citations