Sensitivity to CSF1R inhibitors correlates with MET inhibitor sensitivity and is eliminated after external cytokine stimulation. (A-C) Strong correlation in primary AML patient samples (n = 315) between GW-2580 sensitivity and sensitivity to 3 MET inhibitors: (A) crizotinib, (B) foretinib, and (C) SGX-523. Significance determined by Spearman rank correlation. (D-G) GW-2580 dose-response curves for 4 primary AML patient samples treated with recombinant HGF (1 µg/mL), HS-5–conditioned media, or untreated. Error bars represent mean plus or minus the standard error of the mean (n = 4 replicates); nonlinear curve fitting conducted using least squares regression. Significance determined by 1-way analysis of variance on the area under each curve with the Dunn test for multiple comparisons. (H) Model of CSF1R inhibitor sensitivity in primary AML patient samples resulting from paracrine secretion of cytokines by CSF1R-expressing supportive cells.