Targeting Notch produced a significant anticancer effect in T-ALL with prominent Notch activation (Koch and Radtke, 2011); however, T-ALL with PTEN mutations did not respond to the treatment (Palomero et al., 2007; Hales et al., 2014), demonstrating that Notch-induced PTEN inhibition is essential for T-ALL cell survival. Here, PTEN is linked to acute lymphoblastic leukemia.