Inhibition of BCR-mediated signaling by ARQ 531.

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Inhibition of BCR-mediated signaling by ARQ 531. Inhibition of BCR-mediated signaling by ARQ 531. A, Rosette-Sep isolated primary CLL cells were treated with escalating concentrations of ARQ 531 for 1 hour and then stimulated with anti-IgM for 15 minutes. Immunoblotting was then performed to show that ARQ 531 inhibits phosphorylation of BTK, AKT, and ERK. B, Immunoblot data from 5 patients with CLL treated with ARQ 531 were quantitated using densitometry software. C, Primary CLL cells from 3 patients were treated in vitro with ARQ 531 and ibrutinib to contrast the effect on proximal BCR-associated kinases including Src family members and SYK as well as downstream kinases including MEK and ERK. D, Rosette-Sep isolated primary CLL cells were assessed via immunoblot for transphosphorylation of Y551 following ARQ 531 treatment for 1 hour and anti-IgM stimulation for 15 minutes. For all experiments, differences were assessed using linear mixed-effects models (**, 0.01 ≥ P ≥ 0.001; ***, P < 0.001). Sean D. Reiff et al. Cancer Discov 2018;8:1300-1315 ©2018 by American Association for Cancer Research