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Title: Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma
Authors: Ang, Daniel Aron
Carter, Jean-Michel
Deka, Kamalakshi
Tan, Joel H. L.
Zhou, Jianbiao
Chen, Qingfeng
Chng, Wee Joo
Harmston, Nathan
Li, Yinghui
Keywords: Medicine, Health and Life Sciences
Issue Date: 2024
Source: Ang, D. A., Carter, J., Deka, K., Tan, J. H. L., Zhou, J., Chen, Q., Chng, W. J., Harmston, N. & Li, Y. (2024). Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma. Nature Communications, 15(1), 2513-.
Project: NRF-NRFF2018-04 
Journal: Nature Communications 
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.
ISSN: 2041-1723
DOI: 10.1038/s41467-024-46728-4
Schools: School of Biological Sciences 
Organisations: Institute of Molecular and Cell Biology, A*STAR 
Rights: © The Author(s) 2024. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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