High dose dasatinib treatment markedly reduces the numbers of B-lineage cells.

<p>c-Cbl RING finger mutant mice aged 8–9 months were dosed daily with 30 mg/kg (am) +50 mg/kg (pm) of dasatinib or vehicle, and analyzed after 4 weeks. (A) Numbers of nucleated bone marrow cells from each group. (B) Bone marrow cells analyzed by flow cytometry to determine the percentage of CD11b⁺ myeloid-lineage cells; CD19⁺ B-lineage cells; lineage negative cells (Lin⁻); c-Kit⁺ lineage negative (LK) cells; Lin⁻ Sca-1⁺ c-Kit⁺ (LSK) cells; and multi-potent progenitors (MPPs). (C) Spleen weights from each treatment group. (D) Spleen cells analyzed by flow cytometry to determine percentages of CD11b⁺, CD19⁺ and T cell receptor⁺ (TCR) cells. All of the above data are from 4 dasatinib and 4 vehicle treated mice. The results are expressed as means ± standard errors. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 using the unpaired Student’s <i>t</i> test. (E) H&E stained sections of spleens showing the effects of dasatinib in markedly reducing the size of the follicles in the white pulp. The images were acquired at room temperature using an Olympus BX51 microscope. Photomicrographs were taken at 40× and 200× magnification with 4×/0.16 and 20×/0.70 objective lenses using an Olympus DP70 digital camera. Scale bars are 2 mm and 200 μm respectively.