Figure 3
Figure 3. INCB018424 treatment improves viability and splenomegaly in a JAK2V617F-driven model of malignant disease. (A) Kaplan-Meier analysis of mice inoculated intravenously with Ba/F3-EpoR-JAK2V617F cells and treated with INCB018424 or vehicle (orally, twice a day). (B) Survival was significantly improved with INCB018424 treatment (n = 14 mice/group; P < .001, log-rank test). Effects of JAK inhibition on spleen weights were assessed in a separate cohort of animals treated for 2 weeks with vehicle or INCB018424 (n = 6 /group; P < .001; 2-sided t test). Group means are represented by horizontal bars. (C) Quantitative genomic PCR analysis demonstrated a preferential diminution of cells expressing JAK2V617F after treatment with INCB018424 for 2 weeks (P < .01, 2-sided t test). (D) Phospho-STAT3 assay was performed on spleen lysates collected 4 hours after dosing using the Milliplex MAP system (Millipore), normalized to total protein, and read on a Luminex 200 instrument (Luminex).

INCB018424 treatment improves viability and splenomegaly in a JAK2V617F-driven model of malignant disease. (A) Kaplan-Meier analysis of mice inoculated intravenously with Ba/F3-EpoR-JAK2V617F cells and treated with INCB018424 or vehicle (orally, twice a day). (B) Survival was significantly improved with INCB018424 treatment (n = 14 mice/group; P < .001, log-rank test). Effects of JAK inhibition on spleen weights were assessed in a separate cohort of animals treated for 2 weeks with vehicle or INCB018424 (n = 6 /group; P < .001; 2-sided t test). Group means are represented by horizontal bars. (C) Quantitative genomic PCR analysis demonstrated a preferential diminution of cells expressing JAK2V617F after treatment with INCB018424 for 2 weeks (P < .01, 2-sided t test). (D) Phospho-STAT3 assay was performed on spleen lysates collected 4 hours after dosing using the Milliplex MAP system (Millipore), normalized to total protein, and read on a Luminex 200 instrument (Luminex).

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