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Biomedicines 2018, 6(2), 59;

The NF-κB Activating Pathways in Multiple Myeloma

Systems Immunology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India
Present Address: La Jolla Institute of Allergy and Immunology, La Jolla, CA 92037, USA.
Author to whom correspondence should be addressed.
Received: 12 March 2018 / Revised: 14 May 2018 / Accepted: 14 May 2018 / Published: 16 May 2018
(This article belongs to the Special Issue Roles of NF-κB in Cancer and Their Therapeutic Approaches)
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Multiple myeloma(MM), an incurable plasma cell cancer, represents the second most prevalent hematological malignancy. Deregulated activity of the nuclear factor kappaB (NF-κB) family of transcription factors has been implicated in the pathogenesis of multiple myeloma. Tumor microenvironment-derived cytokines and cancer-associated genetic mutations signal through the canonical as well as the non-canonical arms to activate the NF-κB system in myeloma cells. In fact, frequent engagement of both the NF-κB pathways constitutes a distinguishing characteristic of myeloma. In turn, NF-κB signaling promotes proliferation, survival and drug-resistance of myeloma cells. In this review article, we catalog NF-κB activating genetic mutations and microenvironmental cues associated with multiple myeloma. We then describe how the individual canonical and non-canonical pathways transduce signals and contribute towards NF-κB -driven gene-expressions in healthy and malignant cells. Furthermore, we discuss signaling crosstalk between concomitantly triggered NF-κB pathways, and its plausible implication for anomalous NF-κB activation and NF-κB driven pro-survival gene-expressions in multiple myeloma. Finally, we propose that mechanistic understanding of NF-κB deregulations may provide for improved therapeutic and prognostic tools in multiple myeloma. View Full-Text
Keywords: NF-κB; multiple myeloma; canonical; non-canonical; mutations; microenvironment; cytokines; crosstalk; gene-expressions NF-κB; multiple myeloma; canonical; non-canonical; mutations; microenvironment; cytokines; crosstalk; gene-expressions

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Roy, P.; Sarkar, U.A.; Basak, S. The NF-κB Activating Pathways in Multiple Myeloma. Biomedicines 2018, 6, 59.

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