Moreover, activation of Notch signaling by the T cell in the tumor microenvironment was demonstrated as key mediator of Akt-induces RT (Richter’s transformation), which is an aggressive lymphoma that occurs upon progression from chronic lymphocytic leukemia (CLL), suggesting the critical role of Notch signaling in RT transformation (Kohlhaas et al., 2021). This evidence concerns the gene AKT1 and B-cell chronic lymphocytic leukemia.