The NF-?B Activating Pathways in Multiple Myeloma.

ABSTRACT: Multiple myeloma(MM), an incurable plasma cell cancer, represents the second most prevalent hematological malignancy. Deregulated activity of the nuclear factor kappaB (NF-?B) 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-?B system in myeloma cells. In fact, frequent engagement of both the NF-?B pathways constitutes a distinguishing characteristic of myeloma. In turn, NF-?B signaling promotes proliferation, survival and drug-resistance of myeloma cells. In this review article, we catalog NF-?B 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-?B -driven gene-expressions in healthy and malignant cells. Furthermore, we discuss signaling crosstalk between concomitantly triggered NF-?B pathways, and its plausible implication for anomalous NF-?B activation and NF-?B driven pro-survival gene-expressions in multiple myeloma. Finally, we propose that mechanistic understanding of NF-?B deregulations may provide for improved therapeutic and prognostic tools in multiple myeloma.

SUBMITTER: Roy P 

PROVIDER: S-EPMC6027071 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature