Figure 1. PTEN loss disrupts the circuitry controlling oncogenic cell growth in T-ALL downstream of NOTCH1 in T-ALL.
A. NOTCH1 controls leukemic cell growth through multiple overlapping mechanisms including activation of target genes, upregulation of MYC and downregulation of PTEN via HES1. B. Mutational loss of PTEN induces constitutive activation of AKT and uncouples NOTCH1 signaling from the PI3K-AKT pathway. Thus, PTEN-null T-ALL cells become insensitive to inhibition of NOTCH1 signaling with GSIs.