Fig. 4: The JAK2 p.G993A mutation confers resistance to the type-II JAK inhibitor, CHZ-858. | npj Precision Oncology

Fig. 4: The JAK2 p.G993A mutation confers resistance to the type-II JAK inhibitor, CHZ-858.

From: Acquired JAK2 mutations confer resistance to JAK inhibitors in cell models of acute lymphoblastic leukemia

Fig. 4

a pMIG Empty Vector Ba/F3 cells and Ba/F3 cells expressing either non-mutant or RuxR-mutant (JAK2 p.Y931C, p.L983F, p.G993A) ATF7IP-JAK2 were incubated for 72 h with either a DMSO vehicle control or a dose response of the type-II JAK inhibitor, CHZ-868. The percentage of cell death was measured following a 20 min incubation with apoptotic markers and analysis by flow cytometry. Linear regression or non-linear regression models were fit to appropriate normalized data. Error bars indicate SEM over the mean of three biological replicates. b Ba/F3 cells expressing either non-mutant or JAK2 p.G993A-mutant JAK2 fusion genes were incubated in 1 µM of CHZ-858 for 1 h. STAT5 phosphorylation was assessed by intracellular flow cytometry in comparison to JAK2 Ba/F3 cells starved of IL3 for 5 h. Histograms are representative of three biological replicates and the GFP mean fluorescence intensities (MFIs) are shown.

Back to article page