Figure 1

Caspase inhibition rescues JAK2 ^V617F mutant cells from the apoptotic and anti-proliferative effects of the JAK2 inhibitor NVP-BSK805. SET-2 (A) and MB-02 (B) cells were pretreated for 1 hour with increasing concentrations of a pan-caspase inhibitor, followed by treatment for 24 hours with 500 nM NVP-BSK805. PARP cleavage (cleaved PARP is depicted by arrowheads) was assessed by Western blot analysis. β-tubulin was probed for as a loading control. Controls consisted of drug vehicle (DMSO) treated cells (baseline) and NVP-BSK805 treatment in the absence of the pan-caspase inhibitor. Proliferation assays with increasing concentrations of NVP-BSK805 in SET-2 (C) and MB-02 (D) cells were carried out in the absence (empty triangles/solid line) or presence (filled circles/stippled line) of 200 μM pan-caspase inhibitor.