Mer inhibition is sufficient to significantly decrease colony formation and inhibit leukemogenesis in a mouse xenograft model of pre–B-ALL. Equal numbers of (A) 697, (B) REH shControl, and Mer knockdown (shMer1, shMer4) cells were cultured in methylcellulose for 10 days. Mer knockdown cells formed significantly fewer colonies than shControl cells. Mean values and SEs derived from at least 3 independent experiments are shown. (C-D) NSG mice (n = 7 per group) were injected intravenously with 2 × 106 (697) or 3 × 106 (REH) wild-type, shControl, shMer1, or shMer4 cells. (C) Comparison of survival curves for 697 xenografts revealed a significant increase in leukemia-free survival with Mer inhibition (median survival: 46 days for shMer1, 32 days for shMer4) compared with shControl xenografts (median survival: 18 days). No significant difference was observed between 697 xenografts injected with shControl and wild-type (median survival: 16 days) cells. (D) Comparison of survival curves for REH xenografts revealed a significant increase in leukemia-free survival with Mer inhibition (median survival: 33 days for shMer1, 28 days for shMer4) compared with shControl xenografts (median survival: 24 days). No significant difference was observed between REH xenografts injected with shControl and wild-type (median survival 24 days) cells. *P < .05; **P < .01.
