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

Blood. 2007 Apr 1;109(7):2700-7. doi: 10.1182/blood-2006-07-025809.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Hodgkin Disease / physiopathology
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / physiopathology
  • Lymphocytes / physiology
  • Lymphoma / genetics
  • Lymphoma / physiopathology*
  • Lymphoma / therapy
  • Lymphoma, B-Cell / physiopathology
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / physiopathology
  • Lymphoma, Large B-Cell, Diffuse / physiopathology
  • Models, Biological
  • NF-kappa B / physiology*
  • Oncogene Proteins, Viral / physiology
  • Prognosis
  • Signal Transduction / physiology
  • Translocation, Genetic


  • NF-kappa B
  • Oncogene Proteins, Viral