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. Author manuscript; available in PMC: 2016 Jul 13.
Published in final edited form as: Cancer Cell. 2015 Jul 13;28(1):29–41. doi: 10.1016/j.ccell.2015.06.005

Figure 5. CHZ868 with dexamethasone is highly active against CRLF2/JAK2-dependent leukemias in vivo.

Figure 5

Sublethally-irradiated wild-type mice were transplanted with Eμ-CRLF2/Eμ-Jak2 R683G/Pax5+/−/Ts1Rhr B-ALL. After 15 days, mice were treated with vehicle, CHZ868 (CHZ; 30 mg/kg/day by oral gavage), dexamethasone (dex; 1 mg/kg/day IP), or CHZ868 plus dexamethasone (combo). (A) Spleen weight as a percentage of total body weight after 5 days of treatment (n=3 mice/arm). Photograph of representative spleens from mice in each treatment arm are shown. (B) Percentage of human CRLF2+/mouse CD19+ cells in the peripheral blood, spleen, and bone marrow of mice after 5 days of treatment. (C, D) IHC (C, scale bar, 50 μm) and immunoblots (D) of spleens from mice in each treatment arm sacrificed after 5 days of treatment. (E) Survival of mice dosed with the indicated agents from days 15–28 after injection (yellow box). Survival was compared across arms using the log-rank test. (F) Upon engraftment of CRLF2-rearranged BALL PDXs (>2% peripheral blood human CD45+ cells), mice were treated for 5 days and then sacrificed. Normalized peripheral blood blast count (WBC count × %CD45+/CD19+ cells) relative to vehicle-treated controls. Horizontal lines denote the grand mean for each treatment condition. (G) Spleen weight as a percentage of total body weight is shown. Horizontal lines denote the grand mean for each treatment condition. (H) GSEA plots demonstrate enrichment of indicated apoptosis gene sets in PDXs treated with combination compared to CHZ868 alone for 3 days. (I) Representative immunoblotting of spleen lysates from B-ALL-X1 treated in vivo for 5 days with the indicated agents. In all panels of this figure, error bars represent SEM. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. See also Figure S4.