Notch inhibition targets the LIC in Tal1/Lmo2 mouse T-ALLs. Mouse Tal1/Lmo2 T-ALLs with Notch1 mutations were treated with vehicle or GSI for 48 hours in vitro, stained, and analyzed by flow cytometry. Leukemic cells were serially diluted and transplanted into syngeneic mice, and treatment was continued for 3 weeks. GSI was administered using an intermittent dosing regimen,18 and transplanted mice were monitored for disease development. Kaplan-Meier survival curves are shown for 5 mouse T-ALLs. GSI treatment of mouse T-ALLs 1426 and 2544 eliminated LICs, and GSI-treated recipients failed to develop disease (log-rank test: P < .0004 and P < .001, respectively). GSI treatment of 1928 and 3304 reduced LIC activity and significantly extended survival (log-rank test: P < .02 and P < .0003, respectively). GSI treatment had no statistically significant effect on the survival of mice transplanted with leukemic cells from mouse 1007.
