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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-?B 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.

SUBMITTER: Ranuncolo SM

PROVIDER: S-EPMC3488888 | biostudies-other | 2012 Nov

REPOSITORIES: biostudies-other

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Hodgkin lymphoma requires stabilized NIK and constitutive RelB expression for survival.

Ranuncolo Stella M SM Pittaluga Stefania S Evbuomwan Moses O MO Jaffe Elaine S ES Lewis Brian A BA

Blood 20120911 18

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 biop ...[more]

PMID: 22968463

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