dc.creatorGamboa Cedeño, Angélica María
dc.creatorCastillo, Mariángeles
dc.creatorWenming, Xiao
dc.creatorWaldmann, Thomas
dc.creatorRanuncolo, Stella Maris
dc.date.accessioned2020-10-26T15:26:16Z
dc.date.accessioned2022-10-15T15:53:14Z
dc.date.available2020-10-26T15:26:16Z
dc.date.available2022-10-15T15:53:14Z
dc.date.created2020-10-26T15:26:16Z
dc.date.issued2019-06
dc.identifierGamboa Cedeño, Angélica María; Castillo, Mariángeles; Wenming, Xiao; Waldmann, Thomas; Ranuncolo, Stella Maris; Alternative and canonical NF-kB pathways DNA-binding hierarchies networks define Hodgkin lymphoma and Non-Hodgkin diffuse large B Cell lymphoma respectively; Springer; Journal Of Cancer Research And Clinical Oncology; 145; 6-2019; 1437-1448
dc.identifier0171-5216
dc.identifierhttp://hdl.handle.net/11336/116815
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4405495
dc.description.abstractPurpose: Despite considerable evidence that supports the NF-kB role in the immune system and lymphomagenesis, it is unclear whether specific NF-kB dimers control a particular set of genes that account for their biological functions. Our previous work showed that Hodgkin Lymphoma (HL) is unique, among germinal center (GC)-derived lymphomas, with respect to its dependency on Rel-B to survive. In contrast, diffuse large B-Cell lymphoma (DLBCL) including both Activated B-Cell-Like and Germinal Center B-Cell-Like, requires cREL and Rel-A to survive and it is not affected by Rel-B depletion. These findings highlighted the activity of specific NF-kB subunits in different GC-derived lymphomas. Methods: Sequenced chromatin immunoprecipitated DNA fragments (ChIP-Seq) analysis revealed an extensive NF-kB DNA-binding network in DLBCL and HL. The ChIP-Seq data was merged with microarray analysis following the Rel-A, Rel-B or cRel knockdown to determine effectively regulated genes. Results: Downstream target analysis showed enrichment for cell cycle control, among other signatures. Rel-B and cRel controlled different genes within the same signature in HL and DLBCL, respectively. BCL2 was exclusively controlled by Rel-B in HL. Both mRNA and protein levels decreased following Rel-B depletion meanwhile there was no change upon cRel knock-down. BCL2 exogenous expression partially rescued the death induced by decreased Rel-B in HL cells. Conclusion: The Rel-B hierarchical network defined HL and the cRel hierarchical network characterized DLBCL. Each Rel member performs specific functions in distinct GC-derived lymphomas. This result should be considered for the development of targeted therapies that are aimed to selectively inhibit individual NF-kB dimers.
dc.languageeng
dc.publisherSpringer
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s00432-019-02909-z
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00432-019-02909-z
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectDLBCL
dc.subjectGERMINAL CENTER-DERIVED LYMPHOMAS
dc.subjectHODGKIN LYMPHOMA
dc.subjectNF-KB ALTERNATIVE PATHWAY
dc.subjectNON-HODGKIN LYMPHOMA
dc.subjectREL-B
dc.titleAlternative and canonical NF-kB pathways DNA-binding hierarchies networks define Hodgkin lymphoma and Non-Hodgkin diffuse large B Cell lymphoma respectively
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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