{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:49:57Z","timestamp":1793317797056,"version":"4.5.0"},"reference-count":40,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Venetoclax, a Bcl-2 inhibitor, in combination with the hypomethylating agent azacytidine, achieves complete remission with or without count recovery in \u223c70% of treatment-naive elderly patients unfit for conventional intensive chemotherapy. However, the mechanism of action of this drug combination is not fully understood. We discovered that venetoclax directly activated T cells to increase their cytotoxicity against acute myeloid leukemia (AML) in vitro and in vivo. Venetoclax enhanced T-cell effector function by increasing reactive oxygen species generation through inhibition of respiratory chain supercomplexes formation. In addition, azacytidine induced a viral mimicry response in AML cells by activating the STING\/cGAS pathway, thereby rendering the AML cells more susceptible to T cell\u2013mediated cytotoxicity. Similar findings were seen in patients treated with venetoclax, as this treatment increased reactive oxygen species generation and activated T cells. Collectively, this study presents a new immune-mediated mechanism of action for venetoclax and azacytidine in the treatment of AML and highlights a potential combination of venetoclax and adoptive cell therapy for patients with AML.<\/jats:p>","DOI":"10.1182\/blood.2020009081","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T23:55:39Z","timestamp":1615938939000},"page":"234-245","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":160,"title":["Venetoclax enhances T cell\u2013mediated antileukemic activity by increasing ROS production"],"prefix":"10.1182","volume":"138","author":[{"given":"Jong Bok","family":"Lee","sequence":"first","affiliation":[{"name":"Toronto General Hospital Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilshad H.","family":"Khan","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health 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