Treatment of c-Cbl RING finger mutant mice with AC220 results in a significant reduction in peripheral WBCs. Two cohorts of mice were examined, lethally irradiated C57BL/6.CD45.1 mice repopulated with BM cells from a c-Cbl^A/− mouse (CD45.1^A/−; A) and 8- to 9-month-old naturally bred c-Cbl^A/− mice (B). Both cohorts were bled for 5 days before dosing (Pre-Tx) and after 3 and 6 weeks of dosing. Results are from Hemavet analysis of blood collected from the tail vein. Shown are numbers of WBCs, lymphocytes, neutrophils, and monocytes. The blood counts are expressed as means ± SEM. Treatment of both cohorts with AC220 resulted in statistically significant decreases in WBCs, neutrophil, lymphocyte, and monocyte counts compared with the vehicle-treated mice. *P < .05; **P < .01; ***P < .001 using unpaired Student t test. (C) Representative blood films from 2 vehicle- and 2 AC220-treated c-Cbl^A/− mice after 6 weeks of dosing. The identification numbers and sex of the mice are indicated (F, female) and (M, male). The images were acquired at room temperature using an Olympus BX51 microscope with a 60×/0.09 objective and photographed with an SIS 3VCU Olympus digital camera. Scale bar indicates 50 μm.