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Although these regimens produce better clinical results, the vast majority of patients still suffer from disease recurrence or primary drug resistance. Metformin has been demonstrated to induce apoptosis in cancer cells. However, whether it can synergize with venetoclax and the underlying mechanisms of metformin\u2010induced apoptosis are not fully understood. In this study, we investigated the effect of metformin and venetoclax on the growth of AML cells <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. In both Molm13 and THP\u20101 cell lines, metformin and venetoclax synergistically inhibited the proliferation and induced apoptosis of leukaemia cells. Most importantly, the combination of metformin and venetoclax treatment significantly increased the expression levels of the endoplasmic reticulum (ER) stress\u2010related marker CHOP, for example, in AML cell lines. Knockdown of CHOP markedly attenuated the metformin\u2010 and venetoclax\u2010induced cell apoptosis. Moreover, the combination of metformin and venetoclax demonstrated prominent anti\u2010leukaemia effects in xenograft models and bone marrow samples from AML patients. In summary, the combination of metformin and venetoclax showed enhanced anti\u2010leukaemia activity with acceptable safety in AML patients, representing a new combinatorial strategy worth further clinical investigation to treat AML.<\/jats:p>","DOI":"10.1111\/bjh.18968","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T12:00:53Z","timestamp":1688644853000},"page":"971-984","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Metformin sensitizes <scp>AML<\/scp> cells to venetoclax through endoplasmic reticulum stress\u2014<scp>CHOP<\/scp> pathway"],"prefix":"10.1111","volume":"202","author":[{"given":"Lei","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Hematology The First Affiliated Hospital of Jinan University  Guangzhou Guangdong 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