MYC is upregulated in IμHABCL6 animals harboring ibrutinib-resistant DLBCL. (A) Western blot analysis of pBTK (Tyr223) and pCD19 (Tyr531) in purified murine B-cells pretreated with DMSO or ibrutinib (0.5 μM) for 6 hours and stimulated with H₂O₂ for 3 minutes. (B) Western blot analysis of MYC levels in purified tumor B cells from 18- to 20-month-old IμHABCL6 mice. Cells isolated from each animal were divided in 3 aliquots and kept in culture in the presence of DMSO or ibrutinib (0.5 μM) for 24 or 48 hours. (C) Pipeline for ibrutinib treatment in IμHABCL6 mice. Spleen size was assessed by ultrasound in 13- to 21-month-old mice. Mice enrolled in the study were treated with ibrutinib (12 mg/kg per day IP) for 14 days. (D) Spleen length in IμHABCL6 mice measured by ultrasound at day 1 and 14 in animals treated with ibrutinib or vehicle. Data are shown as a bar graph corresponding to the mean of 6 mice ± SD. P values were calculated using 2-tailed Student t test. (E) Representative images of immunohistochemistry analyses of IμHABCL6 mice spleen tissues. Scale bars, 100 μm. H&E, hematoxylin and eosin; n.s., not statistically significant.