Calcium-dependent signalling in B-cell lymphomas

• Published in: Oncogene Vol. 40; no. 45; pp. 6321 - 6328
• Main Authors: Berditchevski, Fedor, Fennell, Eanna, Murray, Paul G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.11.2021; Nature Publishing Group
• Subjects: 631/67/1990; 631/80/86; Apoptosis; B cells; B-cell lymphoma; B-cell receptor; Biological transport; Calcium (extracellular); Calcium ions; Calcium Signaling; Calcium signalling; Cell Biology; Cell differentiation; Cell migration; Cell proliferation; Cellular signal transduction; Chemokine receptors; Chemotherapy; Cytotoxicity; Development and progression; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Epstein-Barr virus; Epstein-Barr Virus Infections - genetics; Epstein-Barr Virus Infections - metabolism; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Herpesvirus 4, Human - pathogenicity; Human Genetics; Humans; Internal Medicine; Lymphocytes B; Lymphoma; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - metabolism; Lymphoma, B-Cell - virology; Lymphomas; Medicine; Medicine & Public Health; Mutation; Oncology; Receptor mechanisms; Review; Review Article; Signal transduction; United Kingdom
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-021-02025-8

Induced waves of calcium fluxes initiate multiple signalling pathways that play an important role in the differentiation and maturation of B-cells. Finely tuned transient Ca +2 fluxes from the endoplasmic reticulum in response to B-cell receptor (BCR) or chemokine receptor activation are followed by more sustained calcium influxes from the extracellular environment and contribute to the mechanisms responsible for the proliferation of B-cells, their migration within lymphoid organs and their differentiation. Dysregulation of these well-balanced mechanisms in B-cell lymphomas results in uncontrolled cell proliferation and resistance to apoptosis. Consequently, several cytotoxic drugs (and anti-proliferative compounds) used in standard chemotherapy regimens for the treatment of people with lymphoma target calcium-dependent pathways. Furthermore, ~10% of lymphoma associated mutations are found in genes with functions in calcium-dependent signalling, including those affecting B-cell receptor signalling pathways. In this review, we provide an overview of the Ca 2+ -dependent signalling network and outline the contribution of its key components to B cell lymphomagenesis. We also consider how the oncogenic Epstein-Barr virus, which is causally linked to the pathogenesis of a number of B-cell lymphomas, can modify Ca 2+ -dependent signalling.