Selumetinib is active in Ras pathway–mutated ALL cells in an orthotopic primagraft model. Graphs showing log of the percent circulating leukemic cells in mice implanted with RAS WT (A,C) or Ras pathway mutant patient blasts (B,D). Mice were treated with either CV or selumetinib twice daily (100 mg/kg for B and 25 mg/kg for D) and the percent of circulating blasts quantified by flow cytometry during and at the end of treatment. Photographs of spleens (E,F) and graphs of spleen weights (G,H) after 30 drug doses of selumetinib in WT primagrafts (E,G) and RAS mutant primagrafts are shown (F,H).