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February 14, 2026HaematologicaOpen Access

EZH2 inhibition overcomes immunomodulatory drug resistance in multiple myeloma via a cereblon-dependent pathway

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Authors

YLYigen LiAWAmy WilsonYCYakinthi Chrisochoidou

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Overview

Experiments demonstrate EZH2 inhibition reduces IRF4 expression in multiple myeloma, suggesting a new treatment approach.

Key Points

  • The study aims to investigate the role of EZH2 inhibition in overcoming drug resistance in multiple myeloma.
  • Utilized KMS-11 and RPMI-8226 myeloma cell lines as models for primary IMID resistance.
  • Assessed the effects of Tazemetostat, an EZH2 inhibitor, on cell viability and IRF4 expression.
  • Examined the CRBN-dependence of the combinatorial effects of EZH2 inhibition with IMiDs/CELMoDs.
  • Combination treatment with Tazemetostat and IMiDs/CELMoDs significantly reduces IRF4 expression.
  • Induces apoptosis and achieves synergistic cell death in resistant myeloma cell lines.
  • EZH2 inhibition specifically affects IMiD/CELMoD treatment pathways, as evidenced by rescued outcomes in IRF4 overexpression.

Cite This Study

Li et al. (2026) studied this question.

synapsesocial.com/papers/699011172ccff479cfe57745https://doi.org/10.3324/haematol.2025.288024
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Also Consider

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

  1. 1EZH2-dependent STAT3 stabilization drives pomalidomide resistance and is targetable by EZH2 inhibition in multiple myeloma2026
  2. 2MYC Inhibition Potentiates CD8+ T Cells Against Multiple Myeloma and Overcomes Immunomodulatory Drug Resistance2024 · 17 citations
  3. 3Abstract 1792: Comprehensive identification of factors involved in the resistance mechanism of a novel cereblon modulator in multiple myeloma cells2026
  4. 4Targeting degradation of IKZF1 and IKZF3 through modulation of the E3 ligase substrates in the context of cellular therapies for multiple myeloma2025 · 7 citations
  5. 5Epigenetic reprogramming via EZH1/2 inhibition enhances T cell-mediated immunotherapies against multiple myeloma2025