CpG ODNs stimulate ALL cells and induce systemic ALL cell death. (A) A199-bearing mice were treated with 300 μg CpG ODN (□), 100 μg CpG ODN (▪), or PBS (○) and monitored for leukemia cells in peripheral blood. Results presented are leukemia burden as percentage of burden for each animal immediately prior to CpG ODN or PBS administration. (B) A199-bearing mice with significant peripheral leukemia burden were treated with PBS (cross-hatched bars), CpG ODN (dark gray bars), or control ODN (diagonally striped bars) and killed 72 to 96 hours later. Organs were harvested and analyzed for the presence of leukemia cells. Results are presented as leukemia burden in treated mice as a percentage of burden in PBS-treated mice. PBS-treated mice are thus 100%. (C) The percentage of annexin V⁺ ALL cells in spleens from CpG ODN-treated and control-treated (PBS and control ODN) mice. (D) NOD/SCID mice bearing A199 leukemia cells were treated with PBS (cross-hatched bars), CpG ODN (dark gray bars), or control ODN (diagonally striped bars) and then killed 72 hours later. CD40 expression by ALL cells was then determined by flow cytometry. All results (except panel A) are presented as mean ± SD for at least 4 mice/group. **P < .005, *P < .05.