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Mechanisms of NF-κB deregulation in lymphoid malignancies.

Semin. Cancer Biol. 39, 3-14 (2016)
Postprint DOI PMC
Open Access Green
Deregulations promoting constitutive activation of canonical and non-canonical NF-κB signaling are a common feature of many lymphoid malignancies. Due to their cellular origin and the pivotal role of NF-κB for the normal function of B lymphocytes, B-cell malignancies are particularly prone to genetic aberrations that affect the pathway. Key positive regulators of NF-κB signaling can act as oncogenes that are often prone to chromosomal translocation, amplifications or activating mutations. Negative regulators of NF-κB have tumor suppressor functions and are frequently inactivated either by genomic deletions or point mutations. Whereas some aberrations are found in a variety of different lymphoid malignancies, some oncogenic alterations are very restricted to distinct lymphoma subsets, reflecting the clonal and cellular origin of specific lymphoma entities. NF-κB activation in many lymphoma cells is also driven by the microenvironment or chronic signaling that does not rely on genetic alterations. A number of drugs that target the NF-κB pathway are in preclinical or clinical development, revealing that there will be new options for therapies in the future. Since each lymphoma entity utilizes distinct mechanisms to activate NF-κB, a major challenge is to elucidate the exact pathological processes in order to faithfully predict clinical responses to the different therapeutic approaches.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords B-cell Receptor ; Lymphoma ; Nf-κb; Chronic Lymphocytic-leukemia; Hodgkin/reed-sternberg Cells; Brutons Tyrosine Kinase; Malt1 Protease Activity; Multiple-myeloma; Paracaspase Malt1; Abc-dlbcl; Reticuloendotheliosis Virus; Linear Ubiquitination; Receptor Engagement
ISSN (print) / ISBN 1044-579X
e-ISSN 1096-3650
Quellenangaben Volume: 39, Issue: , Pages: 3-14 Article Number: , Supplement: ,
Publisher Saunders
Publishing Place Philadelphia, Pa.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)