In another study, Palomero et al. [71] investigated activating Notch mutations in T-cell leukemia (T-ALL) and were able to show that Notch regulates the expression of PTEN (phosphatase and tensin homolog; see Figure 1(a)) through activation of the Notch target gene Hes1 (hairy and enhancer of split-1), which induces the activity of the class I PI3K-AKT signaling pathway in leukemic T cells, but also in normal thymocytes. Here, HES1 is linked to acute lymphoblastic leukemia.