The combination of VS-5584, SCH772984, and ABT-199 shows superior antileukemic activities against primary AML blasts but spares normal hematopoietic progenitor cells. (A) Primary AML patient samples (n = 6) were pretreated with VS-5584 (VS) and SCH772984 (SCH) alone or in combination for 12 h and then ABT-199 was added for an additional 12 h. Mean percent Annexin V+ cells ± SEM are shown. *** indicates p < .001. (B) Primary AML patient samples (n = 3) were cultured with VS, SCH, and ABT-199, alone or in combination as described in panel A, for 24 h and then plated in methylcellulose and incubated for 2 weeks. The number of surviving AML cells capable of generating leukemia colonies (AML-CFUs) was enumerated. Data are presented as mean ± SEM. ** indicates p < .01 and *** indicates p < .001. (C, D) Human CD34+ cord blood cells were treated with VS, SCH, and ABT-199, alone or in combination, as described in panel A. Cells were plated in methylcellulose and incubated for 2 weeks. The number of surviving hematopoietic cells capable of generating colonies was enumerated. The number of BFU-E, CFU-E, CFU-G, CFU-M, CFU-GM, and CFU-GEMM is presented as mean ± SEM (panel C). Total erythroid and myeloid colonies are presented as mean ± SEM (panel D).