BCI in combination with trametinib eradicated the leukemic clones and cured the leukemic mice. (A-C) Mice that received transplantation with wild-type Kit⁺ cells expressing CSF3R^T618I treated with BCI and trametinib alone or in combination. Graphs showing the percent venus-positive cells as a surrogate leukemic burden (A), total WBC levels (B), and survival (C). (D-F) Mice that received transplantation with compound mutation treated with BCI and trametinib alone or in combination. Graphs showing the percent venus-positive cells as a surrogate leukemic burden (D), total WBC level (E), and survival (F). Treatment with trametinib suppresses leukemia but lacked clonal selectivity resulting to cytostatic response. Treatment with BCI lacked both antileukemic response and clonal selectivity. However, a combination of trametinib and BCI not only suppressed the WBC levels but also effectively eradicated the leukemic clones, resulting in cure in both models of CSF3R-induced leukemia. Representative data are from 2 independent experiments (3 mice per group), shown as the means ± SD. ∗P < .05; ∗∗P < .01; and ∗∗∗P < .001.