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

Vardaka, P.; Kemp, B.; Stephenson, S.; Page, E.; Care, MA.; Umpierrez, M.; Annahar, A.; O'Callaghan, E.; Owen, R.; Hodson, DJ.; Doody, GM.; Tooze, RM.

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

All Authors

Vardaka, P.

Kemp, B.

Stephenson, S.

Page, E.

Care, MA.

Umpierrez, M.

Annahar, A.

O'Callaghan, E.

Owen, R.

Hodson, DJ.

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LTHT Author

Care, Matthew
Owen, Roger
Doody, Gina
Tooze, Reuben

LTHT Department

NIHR Leeds Biomedical Research Centre
Oncology
Haematology
Haematological Malignancy Diagnostic Service
Leeds Cancer Centre

Publication Date

2025

Item Type

Journal Article

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.