Fig. 4.

Simultaneous KIT and BCR-ABL inhibition has a synergistic effect in cell cycle suppression and an additive effect in apoptotic induction of KIT-positive MPD cells. (A) NaPP1 (2 μM), imatinib mesylate (2 μM), and ACK45 (10 μg/ml) inhibitor concentrations were added in the combinations shown to BCR-ABL T315A-expressing MPD cells every 24 h, and cell cycle analyses were conducted 48 h after inhibitor addition as described in Materials and Methods. (B) Inhibitor concentrations as shown in A were added in combinations shown to BCR-ABL T315A-expressing MPD cells every 24 h, and levels of annexin V staining were measured 48 h after inhibitor addition as described (26). (C) Concentrations of NaPP1 (2 μM) and imatinib mesylate (2 μM) were added to BCR-ABL T315A-expressing MPD cells, and levels of examined proteins were measured 6 h after inhibitor addition as described in Materials and Methods. Two separate experiments were conducted in duplicate with similar results.