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 ex vivo 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 interpatient sensitivities to single drugs or combinations with the BCL2-inhibitor venetoclax, and intrapatient 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.
Minihane et al. (Wed,) studied this question.