JNK1 inhibition decreases leukemic burden and modulates immune responses in Eµ-TCL1 mice. (A and B) WBC counts or (B) quantity of CLL-like CD19⁺/CD5⁺ cells of TCL1-tg mice treated with vehicle control or the JNK1 inhibitors SP600125 for 3 wk shown before and after treatment (10 mice in each treatment group). (C) 20 C57BL6 mice were sublethally irradiated and transplanted with splenocytes of three diseases TCL1-tg mice and used for treatment experiments after disease development. Graphs show WBC, RBC, platelet (PLT) counts and quantity of CD19⁺CD5⁺ CLL-like cells in the PB after 3 wk of SP600125 or vehicle treatment (n = 10 per group, unpaired t test, *P < 0.05; ***P < 0.001). (D–F) Total number of CD5⁺CD19⁺ cells per spleen (D), spleen weight (E), and liver weight (F) in TCL1-Tx mice after 3 wk of SP600125 treatment (unpaired t test, *P < 0.05; **P < 0.01). (G) Relative protein levels of p-JNK1, p-BCL2, p-cJUN, and pMCL1 in sorted CD5⁺/CD19⁺ cells from spleens of TCL1-Tx mice after 21 d of SP600125 treatment (unpaired t test, *P < 0.05; **P < 0.01). (H) Protein levels of p-JNK1, total JNK1, p-BCL2, total BCL2, p-c-Jun, total c-Jun, p-MCL1 and total MCL1 in sorted CD5⁺/CD19⁺ cells of TCL1-Tx mice after 21 d of SP600125 treatment. (I) Total number of CD5⁺, CD4⁺, and CD8⁺ T cells in spleens of SP600125-treated TCL1-Tx mice. (J) Absolute number of Tregs in the spleens of TCL1-Tx mice after 3 wk of SP600125 treatment (n = 10 per group, unpaired t test, **P < 0.01). (K) CD107a expression as marker for degranulation of CD4⁺ and CD8⁺ T cells in the spleens of TCL1-Tx mice after 21 d of SP600125 treatment (n = 10 mice per group). (L) Graph shows the percentage of B cells (CD19⁺, B220⁺) in spleens of C57/Bl6 mice (n = 5 per group) treated with vehicle control or the JNK1 inhibitor SP600125 for 3 wk. Statistical significance was calculated via a two-tailed unpaired t test (*P < 0.05; **P < 0.01, ***P < 0.001). Source data are available for this figure: SourceData F6.