Acute response of leukemic mice to drug treatment. (A) Dasatinib treatment rapidly reduces leukemia burden. Twelve mice injected intravenously with 2 × 10⁵ LICs were allowed to develop leukemia over a 10-day period. Mice with equal leukemia burdens were randomized into groups of 3 mice, the first of which was left untreated and euthanized when moribund (time 0). Other groups were treated twice a day with dasatinib (10 mg/kg body weight) for 7, 10, or 13 days and euthanized immediately after the indicated times of treatment. Additional treated cohorts were allowed to undergo clinical relapse after dasatinib withdrawal at day 13 and were moribund by day 22 (see the “Effects of dasatinib, ruxolitinib, and dexamethasone during induction therapy” section). Bone marrow cells (top) and splenocytes (bottom) were harvested for TaqMan qPCR analysis performed with primers directed to the vector-containing Luc2 gene. The fraction of leukemic cells was interpolated from a standard curve created by mixing cultured BCR-ABL+, Arf^−/− LICs with nucleated cells from BM or spleen at defined ratios (supplemental Figure 1). (B) Dexamethasone (Dex), but not ruxolitinib, reduces leukemic burden during 7-day induction therapy. Mice that received LICs and developed leukemia as in panel A were treated with the indicated drug combinations and euthanized. Because monotherapy with dasatinib for 13 days reduces the frequency of leukemic cells below the limit of detectability (panel A), a 7-day treatment period was chosen to allow any additional effects of ruxolitinib and dexamethasone to be recorded. Leukemia burden in BM (top) and spleen (bottom) was estimated by qPCR (TaqMan) as in panel A. Ruxolitinib treatment alone or in combination with dasatinib had no significant activity in acutely reducing the leukemic burden, whereas dexamethasone potentiated remission induction.