Nevertheless, it remains unknown how focusedantagonism of BCL-2 by ABT-199 will shape the landscape of acquired resistance in AML.In this study, we characterize ABT-199-resistant cell lines generated through chronicdrug exposure to implicate BCL-XL and MCL-1 as the main mediators ofresistance to ABT-199 in AML and demonstrate that combinatorial inhibition ofBCL-2/BCL-XL/MCL-1 can be used to delay or altogether forestall theacquisition of cell-autonomous drug resistance. This evidence concerns the gene BCL2L1 and acute myeloid leukemia.