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Enforced MYC expression directs a distinct transcriptional state during plasma cell differentiation.

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Affiliations

  • 1. Division of Haematology and Immunology, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
      Authors
    • Vardaka P 1
    • Kemp B 1
    • Stephenson S 1
    • Page E 1
    • Umpierrez M 1
    • Annahar A 1
    • O'Callaghan E 1
    • Doody GM 1
    (8 authors)
  • 2. Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York, UK.
      Authors
    • Care MA 2
    (1 author)
  • 3. Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
      Authors
    • Owen R 3
    • Tooze RM 3, 5
    (2 authors)
  • 4. Welcome MRC Cambridge Stem Cell Institute, Cambridge, UK.
      Authors
    • Hodson DJ 4
    (1 author)
  • 5. Division of Haematology and Immunology, Leeds Institute of Medical Research, University of Leeds, Leeds, UK
      Authors
    • Tooze RM 3, 5
    (1 author)

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Life Science Alliance, 28 Jul 2025, 8(10):e202402814
https://doi.org/10.26508/lsa.202402814 PMID: 40721291 PMCID: PMC12305944

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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.

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    Funding 

    Funders who supported this work.

    Blood Cancer UK (1)

    • Grant ID: 23021

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    Cambridge University | Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge (1)

    • Grant ID: 203151/Z/16/Z

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    Cancer Research UK (3)

    • Grant ID: RCCFEL/100072, A25117

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    • Grant ID: C355/A26819

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    • Grant ID: C7845/A29212

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    National Institute for Health Research (NIHR) (1)

    • Grant ID: NIHR203331

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    National Institute for Health and Care Research (2)

    • Grant ID: BRC-1215-20014

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    • Grant ID: NIHR203331

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    Wellcome Trust

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