Pasqualucci, L. and Klein, U. orcid.org/0000-0002-4789-967X (2022) NF-κB Mutations in Germinal Center B-Cell Lymphomas: Relation to NF-κB Function in Normal B Cells. Biomedicines, 10 (10). 2450. ISSN 2227-9059
Abstract
Most B cell lymphomas arise from the oncogenic transformation of B cells that have undergone the germinal center (GC) reaction of the T cell-dependent immune response, where high-affinity memory B cells and plasma cells are generated. The high proliferation of GC B cells coupled with occasional errors in the DNA-modifying processes of somatic hypermutation and class switch recombination put the cell at a risk to obtain transforming genetic aberrations, which may activate proto-oncogenes or inactivate tumour suppressor genes. Several subtypes of GC lymphomas harbor genetic mutations leading to constitutive, aberrant activation of the nuclear factor-κB (NF-κB) signaling pathway. In normal B cells, NF-κB has crucial biological roles in development and physiology. GC lymphomas highjack these activities to promote tumour-cell growth and survival. It has become increasingly clear that the separate canonical and non-canonical routes of the NF-κB pathway and the five downstream NF-κB transcription factors have distinct functions in the successive stages of GC B-cell development. These findings may have direct implications for understanding how aberrant NF-κB activation promotes the genesis of various GC lymphomas corresponding to the developmentally distinct GC B-cell subsets. The knowledge arising from these studies may be explored for the development of precision medicine approaches aimed at more effective treatments of the corresponding tumours with specific NF-κB inhibitors, thus reducing systemic toxicity. We here provide an overview on the patterns of genetic NF-κB mutations encountered in the various GC lymphomas and discuss the consequences of aberrant NF-κB activation in those malignancies as related to the biology of NF-κB in their putative normal cellular counterparts.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | lymphoma; lymphomagenesis; B cell; B-cell development; germinal center; NF-kappa B signaling pathway; genetic aberration; diffuse large B-cell lymphoma; Hodgkin lymphoma |
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) > Leeds Institute of Medical Research (LIMR) > Division of Haematology and Immunology |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 May 2024 15:26 |
Last Modified: | 10 May 2024 15:26 |
Status: | Published |
Publisher: | MDPI |
Identification Number: | 10.3390/biomedicines10102450 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:212378 |