Figure 7.
Atovaquone impairs AF10 FP-driven leukemogenesis in vitro and in vivo. (A) Immunoblots showing phospho (p) (Y 705) or total (t) STAT3 with increasing indicated micromolar concentrations of atovaquone are shown in CALM-AF10 or MLL-AF10 murine leukemia cells. B-actin is used as a loading control. (B) Viable cells are plotted as a percentage of DMSO-treated cells (y-axis) with indicated concentrations of atovaquone (x-axis). Cells transformed with CALM-AF10, MLL-AF10, MLL-AF9, or Trib2 were used. (C) Number of CFUs with a blast-like or differentiated morphology in DMSO- or (10 μM) atovaquone-treated conditions is shown. *P < .05. **P < .01. (D) Representative image of colonies from CALM-AF10 or MLL-AF10 mouse AML cells treated with DMSO or atovaquone are shown (original magnification ×10). (E) Survival curves from mice injected with the CALM-AF10+ U937 cell line administered vehicle (red) or Mepron (blue), a clinically used formulation of atovaquone, are shown. P value calculated using log-rank t test (Mantel-Cox) and the number of mice (n) in each group are indicated.