TRC105 treatment alone suppresses the in vivo progression of AML, but not of ALL. (A) Schematic representation of experimental design. Sublethally irradiated NSG mice were IV injected with human AML/ALL blast cells (5 × 105 and 4 × 104 cells, respectively) isolated from the BM of primary recipient mice that had been injected with primary human leukemic blasts. Once hCD45+ cells were detected in the PB, 4 weeks after injection, mice were randomly divided into groups (n = 7 each) and treated with TRC105 or IgG isotype control. (B-D) Effect of TRC105 treatment on AML progression. (B) Representative FACS plots show levels of hCD45 in the PB before (fourth week) and after (eighth and 12th week) treatment with TRC105 or IgG isotype control. (C) Percentage of hCD45+ cells in PB. Bars represent average percentage of hCD45, and error bars indicate SEM for each cohort (n = 7). Leukemia progression was inhibited and actually regressed at week 8 in the TRC105-injected cohort (red), and remained low by week 12 (C). ***P < .001 by ANOVA. (D) TRC105-treated mice exhibited prolonged survival compared with IgG-injected control. Each data point represents a single mouse from TRC105- (red) or IgG isotype- (gray) injected cohort. *P < .05 by log-rank test. (E-G) Effect of TRC105 treatment on ALL progression. (E) Representative FACS plots show levels of hCD45 before (fourth week) and after (eighth week) treatment with TRC105 or IgG isotype control. (F) Bars represent average percentage of hCD45 in PB, and error bars indicate SEM for each cohort (n = 7). Leukemia progressed similarly in both groups. ***P < .001 by ANOVA. (G) No significant differences were observed on survival between TRC105 (red) and IgG isotype-treated groups (gray). Each data point represents a single mouse for each cohort.
