FIGURE 4 from Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation

c-Myc and Mcl-1 are downregulated through enhanced proteasomal degradation. A and B, Ba/F3-ITD, MV4-11, and MOLM-14 cells plated at 1 × 105 cells/mL were treated with 100 µg/mL CHX for 1 hour to inhibit protein synthesis, with or without addition of the proteasome inhibitor MG-132 after 30 minutes, prior to treatment with gilteritinib and/or AZD1208 at same concentrations as in Fig. 3, or DMSO control. Samples collected at serial timepoints were studied for expression of c-Myc (A), Mcl-1 (B) and vinculin loading control protein by immunoblotting. Data in A and B are shown graphically and numerically in C and D, respectively.