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Cells 2018, 7(11), 189; https://doi.org/10.3390/cells7110189

Aberrant Activation of NF-κB Signalling in Aggressive Lymphoid Malignancies

Experimental Haematology, Leeds Institute of Medical Research at St. James’s, School of Medicine, University of Leeds, Leeds LS9 7TF, UK
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Received: 12 October 2018 / Revised: 26 October 2018 / Accepted: 26 October 2018 / Published: 30 October 2018
(This article belongs to the Special Issue NF-κB in Cancer)
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Abstract

Lymphoid malignancies frequently harbor genetic mutations leading to aberrant activation of nuclear factor-κB (NF-κB) signaling; in normal cells, this pathway has important roles in the control of cell growth, survival, stress responses, and inflammation. Malignancies with mutations in NF-κB pathway components can derive from all cell stages of mature B-cell development; however, aberrant NF-κB activity is particularly prevalent in aggressive subtypes of non-Hodgkin lymphoma and myeloma. NF-κB activation is mediated by two separate pathways, the canonical and alternative pathway, and five downstream transcription factor subunits. Recent findings implicate a predominant role for distinct NF-κB pathways and subunits in certain lymphoma subtypes and myeloma; findings which are complemented by the realization that individual NF-κB subunits can have unique, non-redundant biological roles in the putative tumor precursor cells, including activated B cells, germinal center B cells and plasma cells. The knowledge gained from these studies may be exploited for the development of therapeutic strategies to inhibit aberrant NF-κB activity at the level of the transcription-factor subunits and their target genes, as global inhibition of the pathway is toxic. Here, we provide an overview on the role of aberrant NF-κB activation in aggressive lymphoid malignancies and discuss the potential importance of individual NF-κB subunits in the pathogenesis of tumor subtypes. View Full-Text
Keywords: nuclear factor-κB; B-cell lymphoma; germinal center; lymphomagenesis; therapeutic nuclear factor-κB; B-cell lymphoma; germinal center; lymphomagenesis; therapeutic
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Kennedy, R.; Klein, U. Aberrant Activation of NF-κB Signalling in Aggressive Lymphoid Malignancies. Cells 2018, 7, 189.

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