LY2510924 monotherapy has antileukemia activity in OCI-AML3 xenograft models. OCI-AML3/Luc/mCherry cells (1 × 106 per mouse) were intravenously injected into sublethally irradiated (250 cGy) NSG mice. Circulating OCI-AML3 cells were (A) identified by flow cytometry, and (B) percentages were determined among all nucleated cells in mice (n = 3) before and 3 or 24 hours after a single LY2510924 treatment on days 21 and 22. Shown are (C) serial bioluminescence images and (D) intensity quantitation of 5 representative mice from 2 groups, control and LY2510924 (n = 10 each), that began 3 weeks of daily treatment 12 days after cell injection. (E) Three representative mice per group were euthanized on day 22, and tissues were fixed and sectioned for immunohistochemical analysis with antihuman CD45 antibodies to identify human leukemic cells. Analysis of the multispectral images further confirmed that leukemic cell burden was significantly reduced in LY2510924-treated mice. Original magnification, ×200. (F) Overall survival rate in each group was estimated by the Kaplan-Meier method. Results of (D), (E), and (F) are expressed as the mean ± SEM. *P < .05; **P < .01.
