Figure 4.
Ruxolitinib but not pacritinib treatment blocks ITK-SYK–induced TCL and inflammation. GFP (n = 6) and ITK-SYK mice (n = 6) were treated with vehicle (Veh), ruxolitinib (Ruxo; 30 mg/kg body weight; red), or pacritinib (Pacr; 150 mg/kg body weight; green) twice daily for 32 consecutive days for organ analysis and then euthanized. For survival, mice were treated until ITK-SYK+ vehicle group had died (43 days). (A) The 50% inhibitory (IC50) values for ruxolitinib vs pacritinib for human JAK kinases (JAK1-3 and TYK2). (B) Representative images of GFP and ITK-SYK+ mice treated with vehicle, ruxolitinib, or pacritinib for 28 days. Control- and pacritinib-treated mice show loss of fur and skin encrustations as signs of disease. (C) Weight development of mice shown as the changed percentage compared with starting weight on day 0 after transplantation. Statistical significance was calculated for the values on treatment day 28. (D) Phenotypic score of GFP and ITK-SYK mice on treatment day 28. (E) Kaplan-Meier survival curves representing the survival of ITK-SYK mice after treatment with vehicle vs ruxolitinib (left; n = 5) or vehicle vs pacritinib (right; n = 7, vehicle; n = 5, pacritinib) until 46 treatment days. Statistical analysis was performed using the Log-rank Mantel-Cox test. (F) Percentage of CD11b+Ly6G+ neutrophil granulocytes within GFP– PB cells or spleen cells of GFP control and ITK-SYK mice after treatment. Blood samples were taken on treatment day 28 and analyzed by FACS. Spleens were taken on treatment day 32 after transplantation. (G) Representative images of immunohistochemical HRP-DAB staining with anti-CD11b antibody of paraffin-embedded organs of ITK-SYK mice after treatment with vehicle, ruxolitinib, or pacritinib for 32 days. (H) Serum cytokine levels of murine IL-6, IFN-γ, and IL-5 of GFP vehicle (Ctrl) vs ITK-SYK mice after treatment with vehicle (Veh), ruxolitinib (Ruxo), or pacritinib (Pac) on treatment day 32. Bars represent mean values with error bars showing the SEM. Statistical significance was calculated using the Student unpaired t test. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001. Ctrl, control; HRP/DAB, peroxidase detection kit; ns, nonsignificant.

Ruxolitinib but not pacritinib treatment blocks ITK-SYK–induced TCL and inflammation. GFP (n = 6) and ITK-SYK mice (n = 6) were treated with vehicle (Veh), ruxolitinib (Ruxo; 30 mg/kg body weight; red), or pacritinib (Pacr; 150 mg/kg body weight; green) twice daily for 32 consecutive days for organ analysis and then euthanized. For survival, mice were treated until ITK-SYK+ vehicle group had died (43 days). (A) The 50% inhibitory (IC50) values for ruxolitinib vs pacritinib for human JAK kinases (JAK1-3 and TYK2). (B) Representative images of GFP and ITK-SYK+ mice treated with vehicle, ruxolitinib, or pacritinib for 28 days. Control- and pacritinib-treated mice show loss of fur and skin encrustations as signs of disease. (C) Weight development of mice shown as the changed percentage compared with starting weight on day 0 after transplantation. Statistical significance was calculated for the values on treatment day 28. (D) Phenotypic score of GFP and ITK-SYK mice on treatment day 28. (E) Kaplan-Meier survival curves representing the survival of ITK-SYK mice after treatment with vehicle vs ruxolitinib (left; n = 5) or vehicle vs pacritinib (right; n = 7, vehicle; n = 5, pacritinib) until 46 treatment days. Statistical analysis was performed using the Log-rank Mantel-Cox test. (F) Percentage of CD11b+Ly6G+ neutrophil granulocytes within GFP– PB cells or spleen cells of GFP control and ITK-SYK mice after treatment. Blood samples were taken on treatment day 28 and analyzed by FACS. Spleens were taken on treatment day 32 after transplantation. (G) Representative images of immunohistochemical HRP-DAB staining with anti-CD11b antibody of paraffin-embedded organs of ITK-SYK mice after treatment with vehicle, ruxolitinib, or pacritinib for 32 days. (H) Serum cytokine levels of murine IL-6, IFN-γ, and IL-5 of GFP vehicle (Ctrl) vs ITK-SYK mice after treatment with vehicle (Veh), ruxolitinib (Ruxo), or pacritinib (Pac) on treatment day 32. Bars represent mean values with error bars showing the SEM. Statistical significance was calculated using the Student unpaired t test. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001. Ctrl, control; HRP/DAB, peroxidase detection kit; ns, nonsignificant.

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