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]. Here, TP53 is linked to B-cell chronic lymphocytic leukemia.