Figure 2
Figure 2. BV173 engrafted xenograft NSG mouse model treated with dasatinib at doses above the MTD. Error bars show the fifth and 95th percentiles. (A) Leukemic growth measured by BLI in mice treated with high-dose dasatinib therapy (40 mg/kg × 8 days, then lowered to 20 mg/kg ×3 days for a total 11 days of treatment and then stopped altogether secondary to high toxicity), ESKM for 4 weeks only, combination therapy, and control (no therapy). (B) BLI on day 55, 3 weeks after the end of therapy. Mouse #1 in dasatinib with ESKM combination died of dasatinib toxicity on day 13, and mouse #4 appeared to have relapsed in CNS. (C) The high-dose dasatinib plus ESKM group BLI images, showing progression of relapse in mouse #4. (D) Leukemic growth measured by BLI in mice treated with dasatinib therapy at 20 mg/kg IP daily given ×18 days and then stopped owing to high toxicity. ESKM was given to 6 mice (days 18 to 42). All mice relapsed, although ESKM mice relapsed significantly more slowly, and lifespan was longer ×1 week. The last point on each line pertains to when the mice were sacrificed because of illness. (E) BLI at the end of ESKM therapy (day 42). Two cages of mice received ESKM after discontinuation of dasatinib (dasatinib → ESKM 1 and 2) and compared with 1 cage (5 mice) that received no additional therapy. ESKM-salvaged mice have substantially less tumor burden then dasatinib-only mice, although all mice eventually relapsed.

BV173 engrafted xenograft NSG mouse model treated with dasatinib at doses above the MTD. Error bars show the fifth and 95th percentiles. (A) Leukemic growth measured by BLI in mice treated with high-dose dasatinib therapy (40 mg/kg × 8 days, then lowered to 20 mg/kg ×3 days for a total 11 days of treatment and then stopped altogether secondary to high toxicity), ESKM for 4 weeks only, combination therapy, and control (no therapy). (B) BLI on day 55, 3 weeks after the end of therapy. Mouse #1 in dasatinib with ESKM combination died of dasatinib toxicity on day 13, and mouse #4 appeared to have relapsed in CNS. (C) The high-dose dasatinib plus ESKM group BLI images, showing progression of relapse in mouse #4. (D) Leukemic growth measured by BLI in mice treated with dasatinib therapy at 20 mg/kg IP daily given ×18 days and then stopped owing to high toxicity. ESKM was given to 6 mice (days 18 to 42). All mice relapsed, although ESKM mice relapsed significantly more slowly, and lifespan was longer ×1 week. The last point on each line pertains to when the mice were sacrificed because of illness. (E) BLI at the end of ESKM therapy (day 42). Two cages of mice received ESKM after discontinuation of dasatinib (dasatinib → ESKM 1 and 2) and compared with 1 cage (5 mice) that received no additional therapy. ESKM-salvaged mice have substantially less tumor burden then dasatinib-only mice, although all mice eventually relapsed.

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