Intensity of dasatinib therapy correlates with enhanced survival but fails to provide durable remissions when initiated in mice harboring high leukemic burdens. (A) Kaplan-Meier curves representing the overall survival of 4 cohorts of recipient mice that received 2 × 105Arf−/−p185+luc+ LICs 10 days before the start of dasatinib therapy (n = 8 per treatment arm). As indicated in the inset legend, mice received vehicle alone, twice-daily dasatinib therapy 7 days per week (b.i.d. 7/7) or 5 days per week (b.i.d. 5/7), or once-daily dasatinib therapy 7 days per week (q.d. 7/7) or 5 days per week (q.d. 5/7). (B-E) Ten days after LIC inoculation, mice in each cohort evidenced similar degrees of advanced disease as determined by image signal intensities. Whole-animal luminescent signals (photons/s/cm2/sr) for individual recipient mice are plotted as solid lines that depict image intensity (ordinate) versus time in days after injection of LICs (abscissa). The empirically determined lower limit of sensitivity for whole-animal luminescence is indicated by the dotted horizontal line at the bottom of each panel. Therapy was continued throughout the intervals designated by gray shading. Representative inset images reveal localized disease in the neck area (cervical lymph nodes) in the twice-daily 7/7 treatment group (B), in contrast to the disseminated disease including the hind limbs (bone marrow compartment) in the once-daily 5/7 cohort (E).
