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December 8, 2025BloodOpen Access

NSD2 inhibition suppresses t(4;14) gene expression and oncogenic signaling to impair proliferation in multiple myeloma

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Authors

RCRobert S. ChavezTCTerry Connolly

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Overview

Experimental approaches reduce gene expression and growth in multiple myeloma, suggesting chromatin remodeling plays a key role.

Key Points

  • This research focuses on the role of NSD2 in promoting oncogenic signaling and proliferation in multiple myeloma.
  • Used pharmacologic inhibition and CRISPR/Cas9 to investigate NSD2 effects on MM cell lines.
  • Conducted growth assays and assessed chromatin features using immunoblot and RNAseq.
  • Analyzed NSD2-dependent enhancers and gene expression changes through Gene Set Enrichment Analysis.
  • NSD2 inhibition statistically significantly reduced growth in most tested multiple myeloma cell lines.
  • Altered gene expression with 54 shared genes dysregulated by NSD2 inhibition.
  • Significant changes in chromatin state and enhancer activity were observed upon NSD2 inhibition.

Cite This Study

Chavez et al. (2025) studied this question.

synapsesocial.com/papers/69362f364fa91c937236d36dhttps://doi.org/10.1182/blood-2025-3956
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Also Consider

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

  1. 1NSD2 expression remodels DNA methylation, creating a targetable epigenetic dependency in t(4;14) multiple myeloma2025
  2. 2Study of NSD2 using a dTAG system reveals their molecular mechanism and oncogenic implications in t(4;14) multiple myeloma2026 · 2 citations
  3. 3NSD2 Degradation Remediates the Oncogenic Cistrome in t(4;14) Multiple Myeloma2026
  4. 4Inhibition of NSD2 in t(4;14) myeloma induces changes in mitochondrial priming2025
  5. 5Pathogenic Mechanisms Activated by NSD2 Translocations in Multiple Myeloma2024