Figure 6: ZEB2 overexpression promotes T-ALL cell survival and can be prevented by blocking IL7R or JAK1/2 inhibition in vitro and in vivo.

(a) The IL-7-dependent pro-survival effect of Zeb2-overexpressing cell lines can be prevented by co-administration of an IL7R-blocking antibody (A7R34), but not by the isotype control IgG. No effects are seen on the survival of the control cell lines. Student’s t-test was used for statistical analysis. (b) The IL-7-dependent pro-survival effect of Zeb2-overexpressing cell lines can be prevented by co-administration of 1 μg per ml Ruxolitinib phosphate (RUX), a JAK1/2 inhibitor. No effects are seen on the survival of the control cell lines. Student’s t-test was used for statistical analysis. (c) RUX effects were accompanied by the loss of the increased levels of phosphorylated P-STAT5 as well as phosphorylated AKT and GSK3β as determined by western blot analysis. Indicated quantifications represent the relative increase of signal compared with the signal observed without IL-7 and RUX administration. Student’s t-test was used for statistical analysis. (d) In vivo administration of the IL7R-blocking A7R34 antibody extended the lifespan of NOD/SCID mice transplanted with 2 × 10⁶ P53/R26-Zeb2^tg/tg cells. The experiments depicted in a–c were performed twice and representative graphs of western blots are shown. Images have been cropped for presentation. Full size images are presented in Supplementary Fig. 12. The experiment in d was performed once, using four mice per group. *P<0.05, **P<0.01 (vs control).