Systemic CpG-Stat3 siRNA treatment induces regression of disseminated AML in mice. C57BL/6 mice were injected intravenously with 1 × 106CMM+ cells. After 2 to 3 weeks when tumors were engrafted (>1%, ranging from 1% to 5% of AML cells in blood), mice were injected 6 times with CpG-Stat3 siRNA or control CpG-Luc siRNA (5 mg/kg) every other day and euthanized 1 day after the last treatment. (A) Stat3 silencing in AML cells isolated from spleen (left panel) or bone marrow (right panel) was confirmed by using western blotting. (B-C) CpG-Stat3 siRNA treatment reduced the percentage of AML cells in various organs. Flow cytometric analysis of GFP+c-Kit+ AML cells in (B, top) bone marrows or (B, bottom) spleens from various groups of mice. Shown are combined results from 6 mice per group; means ± standard error of the mean (SEM). Statistically significant differences between groups are indicated with asterisks: ***P < .001; *P < .05. (D-E) The effect of CpG-siRNA treatments on (D) spleen and (E) bone marrow cellularities. Shown are (D) representative spleen sizes or (E) histochemical analysis of bone marrow structure in indicated groups of mice. Similar results were derived from 3 independent experiments.
