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Recent advancements in therapeutic strategies, such as targeted therapies to inhibit AML dependencies, have aimed to improve outcomes. The evasion of apoptosis, regulated by the B\u2010cell lymphoma 2 (BCL2) family of proteins, is a key feature of cancer progression and treatment resistance. Bcl\u20102 homology domain 3 (BH3) mimetics, such as venetoclax (ABT\u2010199), which targets BCL2, have shown promising activity in AML. This study investigates for the first time the therapeutic potential of MIK665, a BH3 mimetic targeting myeloid cell leukaemia\u20101 (MCL1), in paediatric AML. We evaluated the efficacy of MIK665 against a diverse panel of AML cell lines and demonstrated its effectiveness as a single\u2010agent treatment. Additionally, MIK665 showed significant activity against a subset of paediatric AML patient\u2010derived xenografts (PDXs) in both ex\u00a0vivo and in\u00a0vivo experiments, with minimal impact on cardiac tissue pathophysiology. These findings strongly support the clinical advancement of MIK665 for paediatric AML treatment in a precision medicine approach.<\/jats:p>","DOI":"10.1111\/bjh.70596","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T08:45:30Z","timestamp":1780562730000},"page":"491-502","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The myeloid cell leukaemia\u2010\n                    <scp>1<\/scp>\n                    inhibitor\n                    <scp>MIK665<\/scp>\n                    is a potent therapy in preclinical models of paediatric acute myeloid leukaemia"],"prefix":"10.1111","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7394-9282","authenticated-orcid":false,"given":"Patrick","family":"Connerty","sequence":"first","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine UNSW Medicine &amp; Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Colgan","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine UNSW Medicine &amp; Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney  Sydney New South Wales Australia"},{"name":"Kids Cancer Centre, Sydney Children's Hospital  Randwick New South Wales Australia"},{"name":"Clinical Research Division Fred Hutchinson Cancer Center  Seattle Washington USA"},{"name":"Department of Pediatrics University of Washington  Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"El\u2010Najjar","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine UNSW Medicine &amp; Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Henry","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine UNSW Medicine &amp; Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhan","family":"Xie","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine UNSW Medicine &amp; Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Idais","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and IT University of Technology Sydney  Sydney New South Wales Australia"},{"name":"Cardiovascular Regeneration Group Heart Research Institute  Newtown New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Gentile","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and IT University of Technology Sydney  Sydney New South Wales Australia"},{"name":"Cardiovascular Regeneration Group Heart Research Institute  Newtown New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Mao","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine UNSW Medicine &amp; Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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