The importance of PTEN in negatively regulating PI3K/AKT/mTOR signaling in T-cell precursors is directly demonstrated in mice with T-cell-specific deletion of PTEN (Lck-Cre or CD4-Cre x Pten fl/fl), whose thymocytes have increased AKT phosphorylation at Ser473, are hyperplastic, and are susceptible to malignant transformation into lymphoma [32]. This evidence concerns the gene PTEN and lymphoma.