{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T21:53:50Z","timestamp":1794002030990,"version":"4.8.0"},"posted":{"date-parts":[[2025,10,15]]},"group-title":"Cancer Biology","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["CA066996"],"award-info":[{"award-number":["CA066996"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K08CA245209"],"award-info":[{"award-number":["K08CA245209"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R35CA242427"],"award-info":[{"award-number":["R35CA242427"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Predictive biomarkers can potentially meet the need for improved drug assignment in acute myeloid leukemia (AML). Fewer than half of AML patients have actionable mutations: consequently, targeted therapy achieves remission in only a fraction of those who have them. Dynamic BH3 Profiling (DBP), a functional assay, can measure changes in\n                  <jats:italic>ex vivo<\/jats:italic>\n                  drug-induced apoptotic priming in multiple cancers. To assess the feasibility and predictive capacity of DBP in AML, we prospectively tested DBP using a fixed-drug panel in myeloblasts from 92 patients. We generated a database combining genetic and functional annotation. Established AML clinical and genetic prognostic characteristics were associated with drug-induced apoptotic priming. We observed distinct\n                  <jats:italic>inter<\/jats:italic>\n                  patient sensitivities to single drugs or combinations with the BCL2-inhibitor venetoclax, and\n                  <jats:italic>intra<\/jats:italic>\n                  patient apoptotic priming differences based on CD123-expression within distinct cell subpopulations. DBP further predicted the likelihood of remission to chemotherapy and targeted agents, supporting its use to identify optimal personalized therapy.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Statement of significance<\/jats:title>\n                  <jats:p>Dynamic BH3 profiling provides patient-specific drug vulnerability data in real-time to inform prognosis and therapy selection.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key takeaways<\/jats:title>\n                  <jats:list list-type=\"order\">\n                    <jats:list-item>\n                      <jats:p>Dynamic BH3 profiling can be performed on bone marrow and leukemic blood from AML patients in 48 hours.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Known clinical prognostic factors associate with drug-induced apoptotic priming in AML.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Drug-induced apoptotic priming identifies drug vulnerabilities in individual patients and predicts clinical response to chemotherapy and small molecule inhibitors.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.14.682414","type":"posted-content","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T23:40:18Z","timestamp":1760571618000},"source":"Crossref","is-referenced-by-count":4,"title":["Dynamic BH3 profiling predicts clinical outcomes in acute myeloid 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