biostudies-literatureBhola PDNCI NIH HHS3827-3836https://www.ebi.ac.uk/biostudies/studies/S-EPMC5096802biostudies-literatureUnknown126(10)Upfront resistance to chemotherapy and relapse following remission are critical problems in leukemia that are generally attributed to subpopulations of chemoresistant tumor cells. There are, however, limited means for prospectively identifying these subpopulations, which hinders an understanding of therapeutic resistance. BH3 profiling is a functional single-cell analysis using synthetic BCL-2 BH3 domain-like peptides that measures mitochondrial apoptotic sensitivity or "priming." Here, we observed that the extent of apoptotic priming is heterogeneous within multiple cancer cell lines and is not the result of experimental noise. Apoptotic priming was also heterogeneous in treatment-naive primary human acute myeloid leukemia (AML) myeloblasts, and this heterogeneity decreased in chemotherapThe Journal of clinical investigationFunctionally identifiable apoptosis-insensitive subpopulations determine chemoresistance in acute myeloid leukemia.PMC5096802K08 CA204734P01 CA066996P01 CA139980Lindsley RCRyan JAGalinsky IMar BGLetai ABhola PDEbert BLVo TTDeAngelo DJHogdal LJfalseFunctionally identifiable apoptosis-insensitive subpopulations determine chemoresistance in acute myeloid leukemia.Upfront resistance to chemotherapy and relapse following remission are critical problems in leukemia that are generally attributed to subpopulations of chemoresistant tumor cells. There are, however, limited means for prospectively identifying these subpopulations, which hinders an understanding of therapeutic resistance. BH3 profiling is a functional single-cell analysis using synthetic BCL-2 BH3 domain-like peptides that measures mitochondrial apoptotic sensitivity or "priming." Here, we observed that the extent of apoptotic priming is heterogeneous within multiple cancer cell lines and is not the result of experimental noise. Apoptotic priming was also heterogeneous in treatment-naive primary human acute myeloid leukemia (AML) myeloblasts, and this heterogeneity decreased in chemotherap2016-01-01T00:00:00Z2016 Oct2026-05-29T20:44:06.353Z2019-03-27T02:28:18ZS-EPMC50968022759929210.1172/jci8290810.1172/JCI82908