Fig. 4

BETi resistant and less sensitive AML cells retain both dinaciclib sensitivity and dinaciclib / PLX51107 combination effects. (A) MOLM-13 and MV4-11 AML cell lines were serially drugged with 0.5 µM PLX51107 followed by drug washout and recovery for 6 months. (B) Dose-response curves of parental MV4-11 and MOLM-13 versus PLX51107 resistant MV4-11 and less sensitive MOLM-13 generated cell lines following 72-hour treatment with increasing doses of PLX51107 and etoposide. mRNA expression of Wnt co-receptor LRP6 in PLX51107 resistant MV4-11 and MOLM-13 cell lines compared to parental as measured by RT-qPCR. (C) Dose-response curves measured by MTS in MV4-11, PLX51107 resistant MV4-11, MOLM-13, and less sensitive MOLM-13 cell lines exposed to increasing doses of dinaciclib for 4 h, followed by washout and recovery for 72 h. Results are from three replicates. (D) PLX51107 resistant MV4-11 and less sensitive MOLM-13 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