{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Meng X"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["1135-46"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3170956"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(7)"],"pubmed_abstract":["Gamma secretase inhibitors (GSIs) comprise a growing class of compounds that interfere with the membrane-bound Notch signaling protein and its downstream intra-nuclear transcriptional targets. As GSI-I (Z-LLNle-CHO) is also a derivative of a widely used proteosome inhibitor MG-132, we hypothesized that this compound might be active in precursor-B acute lymphoblastic leukemia (ALL) cell lines and patient samples. We found that GSI-I treatment of precursor-B ALL blasts induced apoptotic cell death within 18-24 h. With confirmation using RNA and protein analyses, GSI-I blocked nuclear accumulation of cleaved Notch1 and Notch2, and inhibited Notch targets Hey2 and Myc. Microarray analyses of 207 children with high-risk precursor-B ALL demonstrate that Notch pathway expression is a common featu"],"journal":["Leukemia"],"pubmed_title":["GSI-I (Z-LLNle-CHO) inhibits γ-secretase and the proteosome to trigger cell death in precursor-B acute lymphoblastic leukemia."],"pmcid":["PMC3170956"],"funding_grant_id":["U10 CA098543","U24 CA114766","P50 GM085273","R01 CA114589","CA98543","CA114766","P30 CA118100"],"pubmed_authors":["Girodon F","Willman CL","Wilson BS","Hunger SP","Atlas S","Harvey RC","Matlawska-Wasowska K","Winter SS","Mazel T","Chen IM","Meng X","Ness SA"],"additional_accession":[]},"is_claimable":false,"name":"GSI-I (Z-LLNle-CHO) inhibits γ-secretase and the proteosome to trigger cell death in precursor-B acute lymphoblastic leukemia.","description":"Gamma secretase inhibitors (GSIs) comprise a growing class of compounds that interfere with the membrane-bound Notch signaling protein and its downstream intra-nuclear transcriptional targets. As GSI-I (Z-LLNle-CHO) is also a derivative of a widely used proteosome inhibitor MG-132, we hypothesized that this compound might be active in precursor-B acute lymphoblastic leukemia (ALL) cell lines and patient samples. We found that GSI-I treatment of precursor-B ALL blasts induced apoptotic cell death within 18-24 h. With confirmation using RNA and protein analyses, GSI-I blocked nuclear accumulation of cleaved Notch1 and Notch2, and inhibited Notch targets Hey2 and Myc. Microarray analyses of 207 children with high-risk precursor-B ALL demonstrate that Notch pathway expression is a common featu","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Jul","modification":"2026-05-03T07:06:10.922Z","creation":"2025-07-01T03:05:30.453Z"},"accession":"S-EPMC3170956","cross_references":{"pubmed":["21494254"],"doi":["10.1038/leu.2011.50"]}}