FIGURE 3 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

Concurrent Pim and FLT3 inhibition downregulates c-Myc prior to Mcl-1 protein expression. A, Ba/F3-ITD, MV4-11 and MOLM-14 cells and blasts from a patient with FLT3-ITD AML plated at 1 × 105 cells/mL were treated with gilteritinib (15 nmol/L for Ba/F3-ITD and patient blasts and 10 nmol/L for MV4-11 and MOLM-14) and/or 1 µmol/L AZD1208, or DMSO control. B, Ba/F3-ITD, MV4-11, and MOLM-14 cells were also treated with gilteritinib and/or 1 µmol/L TP-3654, or DMSO control. c-Myc, Mcl-1, and vinculin loading control protein levels were measured by immunoblotting in samples collected at serial timepoints. Data in A and B are shown graphically in C and D, respectively.