Sox4 regulates survival signaling via Bcl-xL and the PI3K-AKT pathway in Ph⁺ ALL. Effects of imatinib-treatment (IM) on phosphorylation status of survival signaling molecules (Stat5, AKT, SRC, RPS6) were compared with effects of Sox4 deletion (A). In the absence of Sox4, activation of AKT (p-AKT^S473), S6 (p-S6^S235/6), and SRC (p-SRC^Y416) were decreased. Effects of Cre-mediated deletion on protein levels of Arf (in the presence and absence of imatinib-treatment) and p53 were studied by Western blot in panels B and C. In panel D, Sox4^fl/fl ALL cells were transduced with an expression vector for Bcl-xL on induction of Cre-mediated deletion of Sox4. The effects of Bcl-xL leukemia cell survival (D) and quantitative analysis (E; P = .004) are shown.