This evidence is corroborated by the results of two different studies, where, on one side, PI3K was found to be constitutively active in all the blood samples of CLL and, on the other side, Akt was hyperactivated in high-risk CLL carrying mutations of NOTCH1 and TP53 and in more than 50% of RS biopsies [40,41]. This evidence concerns the gene NOTCH1 and B-cell chronic lymphocytic leukemia.