Figure 7.

Dasatinib treatment exacerbates splenomegaly of mice inoculated with EBV-LCLs. NOG mice subcutaneously inoculated Akata-LCLs were treated with dasatinib or vehicle (n = 5) as shown in Fig. 6A. (A) The spleens removed at the end of the experiment were photographed. N.C. (negative control) was the spleen from a non-inoculated NOG mouse. The scale bar indicates 10 mm. (B) A spleen weight at the end of the experiment was analyzed. The dashed line shows a weight of the spleen from the non-inoculated NOG mouse. (C) A proportion of human CD19⁺ cells in the spleen and peripheral blood at the end of the experiment was analyzed by flow cytometry. Circles indicate data from each mouse, and horizontal bars indicate means. Detailed gating is described in Fig. S12B,C. (D–G) The spleen was stained with HE (D), EBER-ISH (E), anti-LMP1 Ab (F), and anti-EBNA2 Ab (G). The upper images are of a low-power field (the scale bar indicates 500 μm), whereas the bottom ones are of a high-power field (the scale bar indicates 50 μm). The data are representative of the five mice per group, all of which are shown in Figs. S14–S17. (H) Akata-LCLs were treated with dasatinib in vitro for 3 hours. Subsequently, CCR7 and CXCR4 mRNA levels were analyzed by qPCR (n = 3). Expression levels were normalized to GAPDH. Graphs indicates mean ± SD. Statistical analysis was performed using one-way ANOVA and subsequent Tukey’s HSD method. Values not sharing a common letter are significantly different (p < 0.05). (I) CD11b and Gr-1 expression on the spleen and peripheral blood cells at the end of the experiment were analyzed by flow cytometry. Circles indicates data from each mouse, and horizontal bars indicate means. The dashed lines show data of the spleen from the non-inoculated NOG mouse. Detailed gating is described in Fig. S18. Statistical analysis was performed using Student’s t test (*p < 0.05, **p < 0.01).