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December 8, 2025Blood

CXXC1 is required for IRF4 chromatin binding and expression and regulates cellular fitness in lenalidomide-sensitive and -resistant myeloma cells

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Authors

JTJason TaslimMAMaria AttaMBMarco Bua

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Overview

Transcriptome analysis reveals CXXC1 impacts IRF4 expression, cell proliferation, and lenalidomide resistance in myeloma cells, suggesting therapeutic targeting potential.

Key Points

  • This research examines the role of CXXC1 in regulating IRF4 chromatin binding and expression in myeloma cells.
  • Investigated CXXC1's role through shRNA-mediated knockdown and degron-mediated depletion in myeloma cells.
  • Conducted transcriptome analysis and pathway enrichment studies on CXXC1-depleted cells.
  • Performed ChIP-seq to assess the binding of CXXC1 and IRF4 at gene regulatory regions.
  • Analyzed lenalidomide sensitivity and resistance in derived myeloma cell lines.
  • CXXC1 depletion was toxic to both lenalidomide-sensitive and -resistant cells, affecting IRF4 binding.
  • Transcriptome analysis showed downregulation of IRF4 and MYC, implicating CXXC1 in oncogenic programs.
  • CXXC1's role in regulating chromatin binding suggests it as a potential therapeutic target for multiple myeloma.

Cite This Study

Taslim et al. (2025) studied this question.

synapsesocial.com/papers/69362f514fa91c937236d932https://doi.org/10.1182/blood-2025-571
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Also Consider

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

  1. 1CXXC1-dependent IRF4 activity promotes myeloma cell fitness and sustains lenalidomide resistance2026
  2. 2C-terminal binding protein 2 is a novel tumor suppressor targeting the MYC-IRF4 axis in multiple myeloma2024 · 6 citations
  3. 3PHF19 inhibition increases IMiDs sensitivity by epigenetically regulating IRF4 and MYC in multiple myeloma2025
  4. 4Abstract 7352: CYLD mediated non-canonical RelB NF-κB transcription axis in multiple myeloma2026
  5. 5IRF4 mediates non-enzymatic dependency on IRE1 in Multiple Myeloma cells2024