title: Hodgkin lymphoma requires stabilized NIK and constitutive RelB expression for survival.
abstract: We have analyzed the role of the REL family members in Hodgkin lymphoma (HL). shRNA targeting of each REL member showed that HL was uniquely dependent on relB, in contrast to several other B-cell lymphomas. In addition, relA and c-rel shRNA expression also decreased HL cell viability. In exploring relB activation further, we found stable NF-κB inducing kinase (NIK) protein in several HL cell lines and that NIK shRNA also affected HL cell line viability. More importantly, 49 of 50 HL patient biopsies showed stable NIK protein, indicating that NIK and the noncanonical pathway are very prevalent in HL. Lastly, we have used a NIK inhibitor that reduced HL but not other B-cell lymphoma cell viability. These data show that HL is uniquely dependent on relB and that the noncanonical pathway can be a therapeutic target for HL. Furthermore, these results show that multiple REL family members participate in the maintenance of a HL phenotype.
authors.affiliation: Transcriptional Regulation and Biochemistry Unit, Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20852, USA.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Ranuncolo
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Moses O
authors.initials: MO
authors.lastname: Evbuomwan
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Brian A
authors.initials: BA
authors.lastname: Lewis
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D004791:Enzyme Inhibitors; D017346:Protein Serine-Threonine Kinases; D051841:Transcription Factor RelB; D000097782:NF-kappaB-Inducing Kinase; C497593:RELB protein, human