The Ras pathway is activated in TgERG leukemia. (A) Table summarizing most upregulated pathways in TgERG leukemia compared with WT lin^– cells according to the DAVID functional annotations tool. (B) Analysis of the Ras pathway in protein extracts from the spleens of TgERG mice or WT littermates: Ras-GTP pull-down to visualize the active Ras state (upper panel) and Ras pathway protein expression by Western blotting (lower panel). (C) Absence of mutations in Ras in cDNA prepared from TgERG leukemia cells: representative chromatograms showing K-Ras codons 12 and 13. (D) Growth curve of TgERG leukemia cells treated with escalating doses of FTS (mean ± SEM, n = 3; experiment repeated 3 times). (E) Kaplan-Meier survival curve of NSG mice transplanted with TgERG leukemia cells and treated with FTS by daily gavage starting 4 days after transplantation. FTS treatment at 80 mg/kg significantly prolonged survival of leukemia-bearing NSG mice (median survival = 22.5 and 34 days for mice receiving vehicle or FTS 80 mg/kg, respectively, log-rank P < .0001, n = 6). (F) Depletion of Ras-GTP in mice treated with FTS 80 mg/kg. Protein extracts were prepared from the spleens of 2 NSG mice receiving vehicle control, 2 mice receiving FTS 40 mg/kg, and 2 mice receiving 80 mg/kg. Extracts were used for either Ras-GTP pull-down to detect active Ras levels or for Western blotting to detect total Ras and β-tubulin levels.