Figure 5. Leukemic cells from T-ALL mouse models are sensitivity to 5Z7O.

(A) Cell viability assays of bone marrow cells from Klf4^∆/∆ NOTCH1-induced T-ALL mice after 1 month of transplantation (IC50 3.9 μM, n = 5), non-leukemic Klf4^∆/∆ bone marrow cells (IC50 11.4 μM, n = 5), and Klf4^fl/fl bone marrow cells (IC50 8.7 μM, n = 3). (B) Cell viability assays of thymocytes from leukemic Kras^LSL-G12D/+ .Mb1^Cre/+ mice (IC50 83 nM, n = 4) and age-matched controls (IC50 956 nM, n = 3). Cell viability was measured using an ATP-based assay and expressed as a percentage of the vehicle control (DMSO). IC50 values were calculated using GraphPad Prism. (C) KOPTK1 cells labelled with luciferase were treated in vitro with 5Z7O (3 μM for 3 hours) and same number of viable cells transplanted into NSG mice (n = 5 per group) to monitor disease progression by bioluminescence imaging (BLI). (D) C57BL/6 mice were treated everyday Monday to Friday for two weeks with 5Z7O (15 mg/Kg, intraperitoneal). Mice were monitored for body weight and blood counts to evaluate drug toxicity. (E) NSG mice (n = 4–5 per group) were injected with KOPTK1-luciferase cells and then administered in vivo with 5Z7O (15 mK/Kg). Mice were monitored by BLI. (F) BLI analysis and overall survival (Kaplan Meier). Data are representative of two independent experiments. P = 0.09 (one-tailed Student’s t-test).