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Cited by 13Multiple Myeloma Research and TreatmentsNF-κB Signaling PathwaysGenomics and Chromatin Dynamics

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Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma

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Ang, Daniel A., Carter, Jean-Michel, Deka, Kamalakshi, Tan, Joel H. L., Zhou, Jianbiao, Chen, Qingfeng, Chng, Wee Joo, Harmston, Nathan, Li, Yinghui·2024·Nature Communications
DOI 10.1038/s41467-024-46728-4PMC PMC10957915

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Abstract

In multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro-proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment of cis -regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of these cis -regulatory modules on cell and tumour phenotypes using in vitro and in vivo models, confirming RGS1 as a p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression.

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  • Aberrant non-canonical NF-κB signaling induces changes in the epigenome, enhancing transcriptional processes that promote MM progression.

    “In addition, it has demonstrated that the aberrant non-canonical NF-κB signaling induces changes in the epigenome, enhancing transcriptional processes that promote MM progression [146].”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [146]

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Authors
Ang, D. A., Carter, J.-M., Deka, K., Tan, J. H. L., Zhou, J., Chen, Q., Chng, W. J., Harmston, N., & Li, Y.
Affiliations
  • Nanyang Technological University (SG)
  • Agency for Science, Technology and Research (SG)
  • National University of Singapore (SG)
  • Yale-NUS College (SG)
Corresponding author
Li, Yinghui
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-03-21
Volume
15
Issue
1
Pages
2513-2513
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-46728-4
PMC
PMC10957915
OpenAlex
W4393023156
Cited by
13
References
6
Citations by year
2026: 4 · 2025: 6 · 2024: 3
FWCI
4.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DR-NTU (Nanyang Technological University) (submittedVersion, cc-by)
Funders
  • National Research Foundation Singapore (NRF-NRFF2018-04)
  • MOH | National Medical Research Council (NMRC-OFYIRG16nov044)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
multiple myeloma, p52, super-enhancers, enhancer recruitment, cis-regulatory modules, epigenetic reprogramming, RGS1, bone marrow microenvironment, plasma cell survival, transcriptional reprogramming
MeSH terms
Epigenome, Humans, Multiple Myeloma, Signal Transduction, NF-kappa B, NF-kappa B p52 Subunit, Transcriptome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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