Review in translational hematology Aberrant NF-B signaling in lymphoma: mechanisms, consequences, and therapeutic implications

The transcription factor NF-B is a tightly regulated positive mediator of T- and B-cell development, proliferation, and sur-vival. The controlled activity of NF-B is required for the coordination of physi-ologic immune responses. However, con-stitutive NF-B activation can promote continuous lymphocyte proliferation and survival and has recently been recog-nized as a critical pathogenetic factor in lymphoma. Various molecular events lead to deregulation of NF-B signaling in Hodgkin disease and a variety of T- and B-cell non-Hodgkin lymphomas either up-stream or downstream of the central IB kinase. These alterations are prerequi-sites for lymphoma cell cycling and block-age of apoptosis. This review provides an overview of the NF-B pathway and dis-cusses the mechanisms of NF-B deregu-lation in distinct lymphoma entities with defined aberrant pathways: Hodgkin lym-phoma (HL), diffuse large B-cell lym-phoma (DLBCL), mucosa-associated lym-phoid tissue (MALT) lymphoma, primary effusion lymphoma (PEL), and adult T-cell lymphoma/leukemia (ATL). In addition, we summarize recent data that validates the NF-B signaling pathway as an attractive therapeutic target in T- and B-cell malig-nancies. (Blood. 2007;109:2700-2707) © 2007 by The American Society of Hematolog