Targeting the LYN/HS1 axis in vivo delays disease progression in a transplantable model of CLL. (A) The graph shows the accumulation of CD19⁺CD5⁺Igκ⁺ CLL cells in the PB from mice treated with the vehicle control (n = 4) or 25 mg/kg dasatinib (n = 4), as assessed by cytofluorimetric analysis at day 0, day 6, day 13, day 20, and day 27 (euthanasia) after treatment initiation. Displayed are the means ± SEM of the fold increase of CD19⁺CD5⁺Igκ⁺ cells over time, showing the effect of the drug in reducing PB clonal cell accumulation during the whole treatment period. (B) The dot plot displays the absolute number of total CD19⁺CD5⁺Igκ⁺ CLL cells, quantified by the absolute count and analyzed by flow cytometry, present in the SPs, BM, and MESLNs from mice treated with the vehicle control (n = 4) or 25 mg/kg dasatinib (n = 4). Displayed are the means ± SEM of log-transformed values of total CD19⁺CD5⁺Igκ⁺ cells in each organ, showing significant reduction of organ infiltration after treatment. (C) Flow cytometry stainings of SPs (upper panels), BM (middle panels), and MESLNs (lower panels) of 1 representative mouse treated with the vehicle control (left plots) or 25 mg/kg dasatinib (right plots). The number in each dot plot indicates the percentage of total CD19⁺CD5⁺Igκ⁺ cells among lymphocytes. (D) The graph shows the MFI of phosphorylated SRC-Y416 ± SEM from the intracellular staining on SP preparations from mice treated with the vehicle control (n = 4) or 25 mg/kg dasatinib (n = 4), measured as a surrogate marker for LYN activity and analyzed by flow cytometry on gated CD19⁺CD5⁺ cells. The results show significant reduction of SRC phosphorylation in vivo at the end of treatment. *P ≤ .05, unpaired Student t test; **P ≤ .01; RM-ANOVA.