Figure 7. JNK1 inhibition reduces CLL... | Rockefeller University Press

Figure 7.

$JNK1 inhibition reduces CLL cell expansion in patient-derived xenograft (PDX) mouse models for normal and ibrutinib refractory CLL. (A) HuCLL cells (CD45+CD5+CD19+) in the PB of mice (n = 6 per CLL) xenografted with three different CLLs and treated with vehicle control or SP600125 for 2 wk (pts #34, 60, and 8, unpaired t test, *P < 0.05; **P < 0.01). (B and C) HuCLL cells in the spleen (B) and (C) spleen weight in the same experiment after 2 wk of JNK1 inhibitor treatment of xenografted mice (unpaired t test, *P < 0.05; **P < 0.01). (D and E) Treatment of three BTK-inhibitor refractory CLLs with different concentrations of JNK1 inhibitors (CLL#56, #62, #63, unpaired t test, *P < 0.05; **P < 0.01). (F) Engraftment of a BTK- + SYK-inhibitor refractory CLL (#56): Human CD45+ cell engraftment in the spleen of an SP600125-treated mouse (blue) compared with a vehicle-treated mouse (red). (G) Flow cytometry plots showing the percentage of CLL cells in the spleen after 14 d of SP600125 treatment (vehicle:16.8%; SP600125: 7.21%). (H and I) Absolute number of CLL cells in the blood (H) and (I) in the spleen of xenografted NOG mice after 14 days of the vehicle or SP600125 treatment (n = 6 per group, unpaired t test, *P < 0.05; **P < 0.01). (J) IHC staining for human CD79a in the spleens of CLL xenograft mice after 2 wk of SP600125 treatment (scale bar: 20 µm). (K and L) Spleen and liver weights of CLL-transplanted NOG mice after 14 d of SP600125 treatment (n = 6 per group). Statistical significance was calculated via two-tailed unpaired t test (*P < 0.05; **P < 0.01).$

JNK1 inhibition reduces CLL cell expansion in patient-derived xenograft (PDX) mouse models for normal and ibrutinib refractory CLL. (A) HuCLL cells (CD45⁺CD5⁺CD19⁺) in the PB of mice (n = 6 per CLL) xenografted with three different CLLs and treated with vehicle control or SP600125 for 2 wk (pts #34, 60, and 8, unpaired t test, *P < 0.05; **P < 0.01). (B and C) HuCLL cells in the spleen (B) and (C) spleen weight in the same experiment after 2 wk of JNK1 inhibitor treatment of xenografted mice (unpaired t test, *P < 0.05; **P < 0.01). (D and E) Treatment of three BTK-inhibitor refractory CLLs with different concentrations of JNK1 inhibitors (CLL#56, #62, #63, unpaired t test, *P < 0.05; **P < 0.01). (F) Engraftment of a BTK- + SYK-inhibitor refractory CLL (#56): Human CD45⁺ cell engraftment in the spleen of an SP600125-treated mouse (blue) compared with a vehicle-treated mouse (red). (G) Flow cytometry plots showing the percentage of CLL cells in the spleen after 14 d of SP600125 treatment (vehicle:16.8%; SP600125: 7.21%). (H and I) Absolute number of CLL cells in the blood (H) and (I) in the spleen of xenografted NOG mice after 14 days of the vehicle or SP600125 treatment (n = 6 per group, unpaired t test, *P < 0.05; **P < 0.01). (J) IHC staining for human CD79a in the spleens of CLL xenograft mice after 2 wk of SP600125 treatment (scale bar: 20 µm). (K and L) Spleen and liver weights of CLL-transplanted NOG mice after 14 d of SP600125 treatment (n = 6 per group). Statistical significance was calculated via two-tailed unpaired t test (*P < 0.05; **P < 0.01).

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