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This rearrangement evokes aberrant ecotropic viral integration site 1 (\n                    <jats:italic>EVI1<\/jats:italic>\n                    ) overexpression, which enhances leukaemic stem cell self\u2010renewal and drives chemoresistance. However, the mechanisms by which EVI1 contributes to venetoclax resistance remain unclear. In this study, patients with AML were stratified into the\n                    <jats:italic>EVI1<\/jats:italic>\n                    \u2010high and\n                    <jats:italic>EVI1<\/jats:italic>\n                    \u2010low groups based on transcript levels. The\n                    <jats:italic>EVI1<\/jats:italic>\n                    \u2010high subgroup exhibited significantly inferior clinical outcomes and reduced complete remission rates following chemotherapy or venetoclax\u2010based regimens. Meanwhile, we demonstrated that elevated\n                    <jats:italic>EVI1<\/jats:italic>\n                    expression confers resistance to venetoclax by stabilizing myeloid cell leukaemia 1 (MCL\u20101) through activation of the phosphatidylinositol 3\u2010kinase (PI3K)\/protein kinase B (AKT) signalling pathway in\u00a0vitro. Mechanistically, elevated\n                    <jats:italic>EVI1<\/jats:italic>\n                    levels were associated with increased phosphorylation of MCL\u20101 at threonine 163 (T163pMCL\u20101), thereby stabilizing MCL\u20101 by attenuating its ubiquitin\u2013proteasome\u2010mediated degradation. Importantly, cotreatment with venetoclax and the clinically available AKT inhibitor capivasertib effectively restored sensitivity in both cell lines and patient\u2010derived primary AML samples with high\n                    <jats:italic>EVI1<\/jats:italic>\n                    expression. Overall, our findings reveal a novel molecular mechanism underlying EVI1\u2010mediated venetoclax resistance through PI3K\/AKT\u2010driven MCL\u20101 stabilization and suggest a combination strategy involving AKT inhibition as a promising approach for overcoming therapeutic resistance in this high\u2010risk AML subset.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70530","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:41:37Z","timestamp":1780576897000},"page":"84-95","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AKT inhibitor capivasertib reverses EVI1\u2010driven resistance to venetoclax in acute myeloid leukaemia"],"prefix":"10.1111","volume":"209","author":[{"given":"Jiayin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Hematology The Second Hospital of Dalian Medical University  Dalian China"},{"name":"Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Blood Stem Cell Transplantation Institute, Dalian Key Laboratory of Hematology, Diamond Bay Institute of Hematology The Second Hospital of Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjie","family":"Kui","sequence":"additional","affiliation":[{"name":"Department of Hematology The Second Hospital of Dalian Medical University  Dalian China"},{"name":"Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Blood Stem Cell Transplantation Institute, Dalian Key Laboratory of Hematology, Diamond Bay Institute of Hematology The Second Hospital of Dalian Medical University  Dalian 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Hematopoietic Stem Cell Transplantation and Translational Medicine, Blood Stem Cell Transplantation Institute, Dalian Key Laboratory of Hematology, Diamond Bay Institute of Hematology The Second Hospital of Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Hospital of Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4109-2602","authenticated-orcid":false,"given":"Jinsong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Hematology The Second Hospital of Dalian Medical University  Dalian China"},{"name":"Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Blood Stem Cell Transplantation Institute, 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