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December 8, 2025Blood

NSD2 expression remodels DNA methylation, creating a targetable epigenetic dependency in t(4;14) multiple myeloma

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Authors

DPDoris R. PowellAWArun P. WiitaCMConstantine S. Mitsiades

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Overview

Observational analysis reveals that nsd2-high multiple myeloma shows increased sensitivity to hypomethylating agents, suggesting new treatment pathways.

Key Points

  • NSD2-high multiple myeloma exhibits significantly higher apoptosis when treated with decitabine compared to NSD2-low cells.
  • Gene expression analysis identified a distinct profile of differentially expressed genes in response to hypomethylating agents with 3,599 genes affected.
  • CRISPR/Cas9 and RNAseq methods allowed the assessment of nsd2's role in mediating epigenetic changes in multiple myeloma.
  • Therapy targeting histone methyltransferase may exploit unique dependencies in t(4;14) multiple myeloma, requiring further exploration.

Cite This Study

Powell et al. (2025) studied this question.

synapsesocial.com/papers/69362f514fa91c937236d953https://doi.org/10.1182/blood-2025-572
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Also Consider

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

  1. 1NSD2 inhibition suppresses t(4;14) gene expression and oncogenic signaling to impair proliferation in multiple myeloma2025
  2. 2Inhibition of NSD2 in t(4;14) myeloma induces changes in mitochondrial priming2025
  3. 3Genomic and transcriptomic signatures of extramedullary multiple myeloma reveal possible drivers of therapeutic resistance2025
  4. 4Cyclin D1 beyond the cell cycle: A new role in t(11;14) multiple myeloma2025
  5. 5Combinatorial DNMTs and EZH2 inhibition reprograms the H3K27me3 and DNAme-mediated onco-epigenome to suppress multiple myeloma proliferation2025 · 5 citations