IMTIB   27019
INSTITUTO DE MEDICINA TRASLACIONAL E INGENIERIA BIOMEDICA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Alternative NFkB pathway activity in classic Hodgkin Lymphoma.
Autor/es:
RANUNCOLO, STELLA MARIS; GAMBOA-CEDEÑO ANGÉLICA
Lugar:
CABA
Reunión:
Jornada; VII Jornada de Investigación y 16° Premio Prof. Dr. José Tessler del Hospital Italiano de Buenos Aires.; 2019
Institución organizadora:
Hospital Italiano de Buenos Aires (HIBA).
Resumen:
NFkB is a pleitropic family of transcription factors (TFs) known to play major roles in diverse cell processes such as proliferation, apoptosis and inflammation. It is comprised of two signaling arms: canonical (mediated by dimeric combinations of RELA, cREL, NFKB1) and alternative (mediated by RELB/NFkB2). Despite considerable evidence supporting the role of the REL members in lymphomagenesis, it is not clear whether specific NFKB dimers control a particular set of target genes in distinct germinal center (GC) derived lymphomas. As a first approach to address this issue we performed ChIP-Seq for each REL member in different cell lines model of Non-Hodgkin Lymphoma (NHL) and HL. We included BJAB and HBL1, representing the two Diffuse Large B Cell Lymphoma (DLBCL) subtypes GCB-and ABC respectively, UH01 a HL cell line, as well as in primary human centroblasts. This analysis shaped two network architectures: a RelB hierarchical network in HL and a cREL hierarchy in NHL. Microarray analysis of these cell lines following knockdown of RELA, RELB, or cREL was merged with our ChIP-Seq data. The overlap of RELA, cREL and RELB peaks and the corresponding shRNA downregulated targets suggested that these factors directly controlled regulators of the cell cycle, apoptosis, GC B cell TFs and DNA repair among other gene signatures. In summary, we found that HL is the only GC derived malignancy that depends on RELB for viability, and thus differentiates HL from NHL These data argue that each REL member has specific and unique functions and targets, as we predicted from the lack of similarities in their transactivation domains.