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December 8, 2025BloodOpen Access

EZH2 inhibition synergizes with aiolos/ikaros degradation via coordinated chromatin remodeling and FoxO activation in multiple myeloma

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Authors

AGAnita K. Gandhi

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Overview

Combined Mezigdomide and dexamethasone therapy improves apoptotic signaling in multiple myeloma, suggesting chromatin alterations may overcome treatment resistance.

Key Points

  • This research investigates the synergistic effects of EZH2 inhibition and aiolos/ikaros degradation in multiple myeloma.
  • Evaluated the effects of Mezigdomide and dexamethasone on multiple myeloma cell lines.
  • Employed RNA-sequencing and ChIP-seq to analyze gene expression and chromatin structure.
  • Utilized CRISPR-Cas9 technology to knockout FoxO3 and assess its role in treatment synergy.
  • Combination of Mezigdomide and dexamethasone significantly reduced cell proliferation and viability in myeloma cell lines.
  • RNA-sequencing indicated upregulation of apoptotic gene clusters and downregulation of cell cycle-associated genes.
  • FoxO3 knockout partially reduced the anti-proliferative effects of the combination, implicating its role in the therapeutic synergy.

Cite This Study

Anita K. Gandhi (2025) studied this question.

synapsesocial.com/papers/69362f3a4fa91c937236d3eahttps://doi.org/10.1182/blood-2025-5699
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