GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326738/suppl/GSE326738_cuffnorm_EVI1.xlsxftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326738/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326738GEOGSEfalseAKT inhibitor capivasertib reverses EVI1‑driven resistance to venetoclax in acute myeloid leukaemiaAcute 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.2026/04/08GSE326738GSM9637969GSM9637967GSM9637968GSM9637972GSM9637973GSM9637970GSM9637971GSM9637976GSM9637965GSM9637966GSM9637974GSM963797524676326738Homo sapiens