The Alternative NF-kB activity in Hodgkin Lymphoma

GAMBOA-CEDEÑO, ANGÉLICA; CASTILLO, MARIÁNGELES; OTERO, VICTORIA; SCHUTZ, NATALIA; FANTL, DOROTEA; CUGLIARI, SILVANA; MARTA E. ZERGA; JAUK VITALI, FEDERICO; GARCÍA RIVELLO, HERNÁN; ERICA A. ROJAS BILBAO; NUÑEZ, MYRIAM; RANUNCOLO, STELLA MARIS

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LXVI Reunión Anual de la Sociedad Argentina de Inmunología (SAI), Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS) con la participación de la Sociedad Argentina de; 2018

Sociedad Argentina de Invetsigación Clínica (SAIC).

Refractory and relapsed disease (RRD) is currently the challenge when treating Hodgkin Lymphoma (HL) patients. There is no specific therapy rather than rescue chemotherapy schemes, which fails in 50% of the cases and associates with high risk toxicity. This highlights the need to deeper understand the HL molecular biology and the screening for therapeutic directed-targets. We have previously reported that HL relies on the alternative NFkB pathway, mediated by Rel-B and NIK, to survive. Its constitutive activation seems to be involved in the RRD. We aimed to determine the specific Rel-B target genes in HL. We performed ChIP-Seq in U-H01 human HL cell line for Rel-A, Rel-B, cRel, p50 and p52. We analyzed the +/- 2kb peaks from the gene transcription start site. The +/- 2kb Rel-B peaks were distributed on 4,509 genes, meanwhile the +/- 2kb cRel peaks were on 1,994 and the Rel-A ones on 830 genes. Only 6% of Rel-B peaks overlapped with Rel-A and 11% with cRel. The data was merged with gene expression arrays that compared U-H01 shRel-B transduced-induced vs transduced-uninduced cells. Genes that were up- or down-regulated more than 2-fold and with a p