Aberrant NF-kappaB signaling in lymphoma: mechanisms, consequences, and therapeutic implications.
The transcription factor NF-kappaB is a tightly regulated positive mediator of T- and B-cell development, proliferation, and survival. The controlled activity of NF-kappaB is required for the coordination of physiologic immune responses. However, constitutive NF-kappaB 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-kappaB signaling in Hodgkin disease and a variety of T- and B-cell non-Hodgkin lymphomas either up-stream or downstream of the central IkappaB kinase. These alterations are prerequisites for lymphoma cell cycling and blockage of apoptosis. This review provides an overview of the NF-kappaB pathway and discusses the mechanisms of NF-kappaB 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-kappaB signaling pathway as an attractive therapeutic target in T- and B-cell malignancies.
Jost
Philipp J
PJ
III Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Ruland
Jürgen
J
D006689:Hodgkin Disease / Q000503:physiopathology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000503:physiopathology; D008214:Lymphocytes / Q000502:physiology; D008223:Lymphoma / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy; D016393:Lymphoma, B-Cell / Q000503:physiopathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000503:physiopathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000503:physiopathology; D008954:Models, Biological; D016328:NF-kappa B / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000502:physiology; D011379:Prognosis; D015398:Signal Transduction / Q000502:physiology; D014178:Translocation, Genetic
D016328:NF-kappa B; D009856:Oncogene Proteins, Viral