Figure 2.

TBC3486 treatment sensitizes ALL cells to chemotherapy. (a–c) ALL cells (a) LAX7R; (b) ICN3; (c) SF03) were co-cultured with (right panel) or without OP9 cells (left panel) for 4 days and treated with TBC3486 (25 μM) or THI0012 (25 μM) in combination chemotherapy (VDL: V=0.0005 μM, D=0.005 nM, L=0.0005 IU/ml) in vitro and viability of leukemia cells was determined by trypan blue exclusion *P<0.05; experiments were performed in triplicates. (d) ALL cells (LAX7R) were injected into NSG mice (5 × 10⁴ cells/mouse) and recipient mice were then treated with 10 mg/kg/day TBC3486 or THI0012 control, starting on day 3 post leukemia injection. The daily administrations were split into two intraperitoneal injections per day for 2 weeks. In addition, mice were treated with vincristine (0.5 mg/kg once a week), dexamethasone (8 mg/kg five times a week) and L-asparaginase (800 IU/kg five times a week) for 4 weeks. Kaplan–Meier survival curve was analyzed and MST was calculated for each group: THI0012 (n=3, MST=33 days) (black dashed); TBC3486 (n=7, MST=41 days) (red dashed); THI0012+VDL (n=6, MST=58 days) (black solid); TBC3486+VDL (n=7, MST=82 days) (red solid). *P<0.05, log-rank test.