Fig. 1

PLX51107 and dinaciclib demonstrate both single agent and combination activity in pre-clinical models of AML. (A) Cells from primary AML samples (n = 8) were co-cultured on HS-5 stroma in the presence of increasing concentrations of PLX51107. Relative viability was assessed using an MTS assay after 96 h. (B) Primary AML samples (n = 8) were treated with increasing concentrations of dinaciclib for two hours, followed by washout and plating with stroma. Viability was assessed using an MTS assay 94 h after co-culture. (C) The same primary AML samples (n = 8) were treated with 10 nM or 100 nM dinaciclib for 2 h, followed by washout and stromal co-culture with continuous exposure to 1 µM PLX51107 for 94 h (96 h total). Results are expressed as viability of combination treated cells relative to vehicle control (0.1 µM dinaciclib + PLX51107 vs. vehicle, p ≤ 0.0005). A mixed effects model, incorporating repeated measures for each patient sample was used for statistical analysis. (D) MV4-11, MOLM-13, and OCI-AML3 AML cell lines were treated with a range of doses of dinaciclib and PLX51107 for 72 h, and then, MTS reagent was added and absorption read. Highest single-agent (HSA) analysis was used to visualize regions of synergy. (*, **, *** = p ≤ 0.05, 0.01, and 0.001, respectively). (E) 10,000 cells/mL from primary AML samples (n = 6) were treated with vehicle control, dinaciclib (0.1 µM), PLX51107 (1 µM), or the combination and plated in triplicate in methylcellulose-based media. Colonies were counted after 14 days of incubation and expressed relative to vehicle treatment. (**** = p ≤ 0.0001)