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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 4. CHZ868 synergizes with dexamethasone in CRLF2-rearranged, JAK2-dependent human B-ALL cells.

Figure 4

(A) Isobologram analysis of CHZ868 and dexamethasone at multiple concentrations in MHH-CALL4 cells. Results are from a representative experiment performed in triplicate. CI: combination index. (B) MHH-CALL4 cells were exposed to vehicle, 300 nM CHZ868, 5 nM dexamethasone, or the combination (combo) for 48 hr. Relative cell proliferation was measured using CellTiterGlo. Results are from 18 replicates across 3 experiments. (C) Cells were treated as in (B) and the percentage of cells positive for Annexin V alone (AV+) or both Annexin V and Propidium Iodide (AV+/PI+) in each treatment arm was averaged across 18 replicates from 3 independent experiments. p values are comparing the percentage of negative cells. (D) Immunoblotting for the indicated targets performed on lysates from MHH-CALL4 cells treated with vehicle (DMSO), 300 nM CHZ868, 5 nM dexamethasone, or the combination for 24 hr. (E) Dynamic BH3 profiling was performed in Nalm 6 and MHH-CALL4 cells treated with vehicle, 300 nM CHZ868, 5 nM dexamethasone, or the combination for 16 hr, and then exposed to 0.1 μM BIM. (F) GSEA plots demonstrate enrichment of indicated apoptosis gene sets in MHH-CALL4 treated with the combination of dexamethasone and CHZ868 compared to single-agent CHZ868. In all panels of this figure, error bars represent SEM. *p<0.05, **p<0.01, ***p<0.001. See also Figure S3.