Leukemia-cell infiltration into the brain. (A-D) Formalin-fixed, decalcified, paraffin-embedded sections from the heads of mice were stained with hematoxylin and eosin and examined for the presence of leukemic infiltration of meninges, brain parenchyma, and bone marrow within the overlying calvaria. (A) Coronal sections from moribund, vehicle-treated mice 13 days after receipt of LICs showed characteristically high levels of leukemic-cell infiltration into the meningeal layer associated with filling of bone marrow space in overlying calvaria. (B) At the start (St) of dasatinib therapy 10 days after LIC injection, recipients typically harbored detectable leukemic infiltrates in the meninges. (C) Infiltrates decreased significantly after 1 week (1w) of dasatinib therapy. (D) Significant leukemic expansion was observed in all mice that ultimately relapsed despite continuous dasatinib therapy. (E) Leukemia infiltration of the CNS of recipients was reviewed and scored by a blinded veterinary pathologist from mice at the start of dasatinib therapy (St; n = 4); after 1 week (1w; n = 4), 2 weeks (2w; n = 4), or 3 weeks (3w; n = 4) of twice-daily (5 days per week) dasatinib therapy; or at clinical relapse (Rel; n = 15). This panel depicts the leukemic infiltration score in mice at the indicated times; scores represent the thickest portion of lymphocyte infiltration of all sections reviewed and are expressed in micrometers.