Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA189234 | ENA |
REPOSITORIES: ENA
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Project description:Golcadomide is a potential first-in-class Aiolos/Ikaros-degrading CRBN E3 ligase modulator (CELMoD) agent designed for the treatment of non-Hodgkin lymphoma (NHL) including diffuse large B-cell lymphoma (DLBCL). Aiolos and Ikaros are two critical lineage factors in lymphoid development that sustain lymphoma growth through recruitment of transcriptional complexes to enhancers and promotors of target genes. Through an epigenetic compound library screening, we found that BET inhibitors sensitize DLBCL cells to golcadomide. Using phenotypic assays and a multi-omics approach, we found that the combination treatment led to synergistic inhibition of MYC and E2F target genes, induction of p21, and subsequent cell cycle arrest. Genome-wide analysis revealed co-occupancy of Aiolos, Ikaros and BRD4 at the promoters of MYC and other genes involved in proliferation, as well as MYC-activating enhancers.
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