Dynamic BH3 profiling predicts clinical outcomes in acute myeloid leukemia

Area of Science:

• Hematology
• Oncology
• Biomarker Discovery

Background:

• Acute myeloid leukemia (AML) treatment requires improved drug assignment strategies.
• Targeted therapies benefit only a subset of AML patients due to limited actionable mutations.
• Dynamic BH3 Profiling (DBP) is a functional assay measuring ex vivo drug-induced apoptotic priming.

Purpose of the Study:

• To evaluate the feasibility and predictive capability of DBP in AML.
• To correlate DBP findings with established AML prognostic factors.
• To assess DBP's ability to predict patient response to various therapies.

Main Methods:

• Prospective testing of DBP on myeloblasts from 92 AML patients using a fixed-drug panel.
• Generation of a combined genetic and functional annotation database.
• Analysis of inter- and intra-patient apoptotic priming variations.

Main Results:

• Established AML prognostic factors correlated with drug-induced apoptotic priming.
• Observed distinct patient sensitivities to single agents and venetoclax combinations.
• Identified intra-patient differences in apoptotic priming related to CD123 expression.
• DBP predicted remission likelihood for chemotherapy and targeted agents.

Conclusions:

• DBP is a feasible functional assay for AML.
• DBP reveals patient-specific drug vulnerabilities and predicts therapeutic response.
• DBP supports personalized therapy selection in AML.