{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Eagle K"],"funding":["NCRR NIH HHS","NIDDK NIH HHS","NCI NIH HHS"],"pagination":["386-399.e7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8903199"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(3)"],"pubmed_abstract":["Deregulation of transcription is a hallmark of acute myeloid leukemia (AML) that drives oncogenic expression programs and presents opportunities for therapeutic targeting. By integrating comprehensive pan-cancer enhancer landscapes with genetic dependency mapping, we find that AML-enriched enhancers encode for more selective tumor dependencies. We hypothesized that this approach could identify actionable dependencies downstream of oncogenic driver events and discovered a MYB-regulated AML-enriched enhancer regulating SEPHS2, a key component of the selenoprotein production pathway. Using a combination of patient samples and mouse models, we show that this enhancer upregulates SEPHS2, promoting selenoprotein production and antioxidant function required for AML survival. SEPHS2 and other sele"],"journal":["Cell stem cell"],"pubmed_title":["An oncogenic enhancer encodes selective selenium dependency in AML."],"pmcid":["PMC8903199"],"funding_grant_id":["R01 CA215452","T32 DK060445","R01 CA193235","S10 RR024574","R01 CA255813","P30 CA125123"],"pubmed_authors":["Jiang Y","Hu T","Koren JV","Perez MW","Eagle K","Shi X","Li M","Obholzer NP","Kitano A","Nakada D","Yi JS","Lin CY"],"additional_accession":[]},"is_claimable":false,"name":"An oncogenic enhancer encodes selective selenium dependency in AML.","description":"Deregulation of transcription is a hallmark of acute myeloid leukemia (AML) that drives oncogenic expression programs and presents opportunities for therapeutic targeting. By integrating comprehensive pan-cancer enhancer landscapes with genetic dependency mapping, we find that AML-enriched enhancers encode for more selective tumor dependencies. We hypothesized that this approach could identify actionable dependencies downstream of oncogenic driver events and discovered a MYB-regulated AML-enriched enhancer regulating SEPHS2, a key component of the selenoprotein production pathway. Using a combination of patient samples and mouse models, we show that this enhancer upregulates SEPHS2, promoting selenoprotein production and antioxidant function required for AML survival. SEPHS2 and other sele","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-29T01:19:03.21Z","creation":"2024-11-15T22:18:29.261Z"},"accession":"S-EPMC8903199","cross_references":{"pubmed":["35108519"],"doi":["10.1016/j.stem.2022.01.003"]}}