FIGURE 7 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 inhibitor treatment activates GSK-3β, and GSK-3β inhibitor abrogates c-Myc and Mcl-1 downregulation. A, Ba/F3-ITD cells and FLT3-ITD AML patient blasts were treated with gilteritinib and/or AZD1208, or DMSO control, and expression of c-Myc, Mcl-1, p-GSK-3α,β (S9/S21), GSK-3α,β and β-actin or vinculin loading control at serial time points was measured by immunoblotting. Data in A are shown graphically in B. C, Ba/F3-ITD and MV4-11 cells and FLT3-ITD AML patient blasts were treated with gilteritinib and/or AZD1208, or DMSO control, with and without the GSK-3β inhibitor TC G-24 at 20 nM, and expression of c-Myc, Mcl-1, p-GSK-3α,β (S9/S21), GSK-3α,β and β-actin or vinculin loading control was measured at serial time points by immunoblotting. Data in C are shown graphically in D.