Aberrant NF-κB signaling in lymphoma: mechanisms, consequences, and therapeutic implications

Abstract

The transcription factor NF-κB is a tightly regulated positive mediator of T- and B-cell development, proliferation, and survival. The controlled activity of NF-κB is required for the coordination of physiologic immune responses. However, constitutive NF-κB activation can promote continuous lymphocyte proliferation and survival and has recently been recognized as a critical pathogenetic factor in lymphoma. Various molecular events lead to deregulation of NF-κB signaling in Hodgkin disease and a variety of T- and B-cell non-Hodgkin lymphomas either upstream or downstream of the central IκB kinase. These alterations are prerequisites for lymphoma cell cycling and blockage of apoptosis. This review provides an overview of the NF-κB pathway and discusses the mechanisms of NF-κB deregulation in distinct lymphoma entities with defined aberrant pathways: Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), mucosa-associated lymphoid tissue (MALT) lymphoma, primary effusion lymphoma (PEL), and adult T-cell lymphoma/leukemia (ATL). In addition, we summarize recent data that validates the NF-κB signaling pathway as an attractive therapeutic target in T- and B-cell malignancies.