AC220 treatment of c-Cbl RING finger mutant mice results in a significant reduction of splenomegaly and the loss of invasive myeloid-lineage cells from the liver and lungs. Spleen weights were determined after 6 weeks of daily dosing with vehicle or AC220 of C57BL/6.CD45.1 mice repopulated with BM cells from an 8-week-old c-Cbl^A/− mouse (A) and 8- to 9-month-old naturally bred c-Cbl^A/− mice (B). (C) Photograph of spleens from a vehicle- and an AC220-treated c-Cbl^A/− mouse after 6 weeks of dosing. (D) H&E-stained sections of livers and lungs from c-Cbl^A/− mice 8-9 months of age that were dosed daily for 6 weeks with vehicle or AC220. The AC220-treated mice showed a marked reduction in myeloid cell invasion, with residual regions of infiltrating cells in AC220-treated mice indicated by arrows. The images were acquired at room temperature using an Olympus BX51 microscope with a 2×/0.08 objective and photographed with an SIS 3VCU Olympus digital camera. Scale bar indicates 2 mm.