{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Xlsx":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326738/suppl/GSE326738_cuffnorm_EVI1.xlsx"],"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326738/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326738"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"AKT inhibitor capivasertib reverses EVI1‑driven resistance to venetoclax in acute myeloid leukaemia","description":"Acute myeloid leukaemia (AML) with MECOM rearrangement is recognized by the World Health Organization as a distinct entity characterized by poor prognosis and aggressive disease progression. We demonstrated that elevated EVI1 expression confers resistance to venetoclax by stabilizing MCL‑1 through activation of the PI3K/AKT signalling pathway in vitro. Mechanistically, elevated EVI1 levels were associated with increased phosphorylation of MCL-1 at threonine 163 (T163pMCL‑1), thereby stabilizing MCL-1 by attenuating its ubiquitin–proteasome mediated degradation. Importantly, cotreatment with venetoclax and the clinically available AKT inhibitor capivasertib effectively restored sensitivity in both cell lines and patient-derived primary AML samples with high EVI1 expression. Overall, our findings reveal a novel molecular mechanism underlying EVI1-mediated venetoclax resistance through PI3K/AKT-driven MCL‑1 stabilization and suggest a combination strategy involving AKT inhibition as a promising approach for overcoming therapeutic resistance in this high-risk AML subset.","dates":{"publication":"2026/04/08"},"accession":"GSE326738","cross_references":{"GSM":["GSM9637969","GSM9637967","GSM9637968","GSM9637972","GSM9637973","GSM9637970","GSM9637971","GSM9637976","GSM9637965","GSM9637966","GSM9637974","GSM9637975"],"GPL":["24676"],"GSE":["326738"],"taxon":["Homo sapiens"]}}