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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2700-2707.
Prepublished online as a Blood First Edition Paper on November 21, 2006; DOI 10.1182/blood-2006-07-025809.
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REVIEW IN TRANSLATIONAL HEMATOLOGY
Aberrant NF- B signaling in lymphoma: mechanisms, consequences, and therapeutic implications
Philipp J. Jost1, and
Jürgen Ruland1
1 III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
The transcription factor NF- B is a tightly regulated positive mediator of T- and B-cell development, proliferation, and survival. The controlled activity of NF- B is required for the coordination of physiologic immune responses. However, constitutive NF- B 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- B signaling in Hodgkin disease and a variety of T- and B-cell non-Hodgkin lymphomas either upstream or downstream of the central I B kinase. These alterations are prerequisites for lymphoma cell cycling and blockage of apoptosis. This review provides an overview of the NF- B pathway and discusses the mechanisms of NF- B 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- B signaling pathway as an attractive therapeutic target in T- and B-cell malignancies.

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