Activity of ruxolitinib in ALL xenografts with JAK/STAT pathway activation. Genetic lesions are indicated to the left of each row. (A) Peripheral blast count (PBC) over time. Graphed are means and SDs with PBC × 103 per microliter on the vertical axis and weeks of treatment on the horizontal axis; n indicated in panel B. (B) Splenic blast count (SBC) at sacrifice. Means and SDs are graphed with the vertical axis representing absolute SBC × 106; n for each arm indicated above bar. (C) Levels of phosphorylated STAT5 (pSTAT5) by immunoblot. Xenografts were treated with ruxolitinib (rux) or vehicle (veh) for 72 hours, spleens were harvested, and protein lysates subjected to immunoblot for pSTAT5, total STAT5, and actin. (D) Comparison of basal levels of pSTAT5 in vehicle-treated xenografts. A representative immunoblot for pSTAT5, total STAT5, and actin is shown on the left, and quantitation of pSTAT5 signal intensity (normalized to actin signal intensity and graphed relative to xenograft V) in 3 vehicle-treated xenografts is shown on the right.
