Vardaka, P., Kemp, B., Stephenson, S. et al. (9 more authors) (2025) Enforced MYC expression directs a distinct transcriptional state during plasma cell differentiation. Life Science Alliance, 8 (10). e202402814. ISSN: 2575-1077
Abstract
MYC provides a rheostat linking cell growth and division. Deregulation of MYC drives transformation in aggressive B-cell neoplasms, often accompanied by BCL2-mediated apoptotic protection. We assess how MYC and BCL2 deregulation impacts on the ability of human B cells to complete plasma cell (PC) differentiation. As B cells differentiate, MYC deregulation has little impact on the regulatory circuitry controlling B-cell identity. Induction of transcriptional regulators BLIMP1 and IRF4 remains intact and accompanies loss of B-cell surface markers. However, such differentiating cells develop an aberrant surface phenotype with reduced expression of phenotypic markers of differentiation. Although functional antibody secretion is established, enforced MYC expression dampens the expression of secretory programmes associated with PC differentiation. Accompanying this, diverse changes in the expression of genes related to translation and metabolism are observed. The establishment of this aberrant differentiated state depends on MYC homology box II. This dependence is profound and resolves to residue W135.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 Vardaka et al. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Funding Information: | Funder Grant number Cancer Research UK Supplier No: 138573 ONAG1Z4S Blood Cancer UK 23021 Cancer Research UK Supplier No: 138573 A29212 |
Depositing User: | Symplectic Publications |
Date Deposited: | 25 Jul 2025 10:16 |
Last Modified: | 20 Aug 2025 10:49 |
Status: | Published |
Publisher: | EMBO Press |
Identification Number: | 10.26508/lsa.202402814 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:229579 |