Figure 5.
LY2510924 induces mobilization of OCI-AML3 cells in vivo and enhances antileukemia effects in combination with chemotherapy. OCI-AML3/Luc/GFP cells (1 × 106 per mouse) were intravenously injected into NSG mice. (A) In mobilization studies, percentages of circulating OCI-AML3/Luc/GFP cells before and 3 or 24 hours after the first LY2510924 injection on day 25 in 6 mice were compared with those in untreated mice (n = 6). (B-E) After confirming leukemia engraftment by BLI, mice were divided into 4 groups (10 mice per group) and began to receive treatment on day 8: control (no treatment), chemotherapy (cytarabine [Ara-C]/doxorubicin), LY2510924, or the combination of chemotherapy with LY2510924. Chemotherapeutics were administered 3 hours after LY2510924 administration. Five representative mice from each group were subjected to (B) serial BLI and (C) intensity quantitation on days 7, 26, and 40 after leukemic cell injection. (D) Three representative mice per group were euthanized on day 27 for immunohistochemical analysis for human CD45 to identify human leukemic cells. Analysis of the multispectral images further confirmed the significantly reduced leukemic cell burden in LY2510924-treated mice and even more so in the combination group. Original magnification, ×40. (E) Overall survival rate in each group was estimated by the Kaplan-Meier method. Results of (A) and (C-D) are expressed as the mean ± SEM. *P < .05; **P < .01.