ArticleCancer research2024
Selective Enhancer Gain-of-Function Deregulates MYC Expression in Multiple Myeloma.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The trial behind it
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Who cites it
5 citing papers in PubMed.
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- IRF2 is an essential transcription factor with pathogenic and prognostic impact in multiple myeloma.Blood · 2026Article
- Hi-C for genome-wide detection of enhancer-hijacking rearrangements in routine lymphoid cancer biopsies.Cell genomics · 2026Article
- Selective Enhancer Dependencies in MYC-Intact and MYC-Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma.Blood cancer discovery · 2025Article
- The de novo DNA methyltransferase 3B is a novel epigenetic regulator of MYC in multiple myeloma, representing a promising therapeutic target to counter relapse.Journal of experimental & clinical cancer research : CR · 2025Article
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Authors and funding
14 authors.
Funding
Abstract
MYC deregulation occurs in the majority of multiple myeloma cases and is associated with progression and worse prognosis. Enhanced MYC expression occurs in about 70% of patients with multiple myeloma, but it is known to be driven by translocation or amplification events in only ∼40% of myelomas. Here, we used CRISPR interference to uncover an epigenetic mechanism of MYC regulation whereby increased accessibility of a plasma cell-type-specific enhancer leads to increased MYC expression. This native enhancer activity was not associated with enhancer hijacking events but led to specific binding of cMAF, IRF4, and SPIB transcription factors that activated MYC expression in the absence of known genetic aberrations. In addition, focal amplification was another mechanism of activation of this enhancer in approximately 3.4% of patients with multiple myeloma. Together, these findings define an epigenetic mechanism of MYC deregulation in multiple myeloma beyond known translocations or amplifications and point to the importance of noncoding regulatory elements and their associated transcription factor networks as drivers of multiple myeloma progression. Significance: The discovery of a native developmental enhancer that sustains the expression of MYC in a subset of myelomas could help identify predictive biomarkers and therapeutic targets to improve the outcomes of patients with multiple myeloma.
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Registered trials
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