The genes most frequently affected by molecular alterations in CLL cluster into specific biological pathways, including NOTCH1 signaling (NOTCH1 and FBXW7), DNA damage response (ATM, TP53, POT1), apoptosis (miR15/16 and BCL2), BCR and toll-like receptor (TLR) signaling (EGR2, BCOR, MYD88, TLR2, IKZF3), NF-κB signaling (BIRC3, NFKBIE, TRAF2, TRAF3), and RNA splicing and metabolism (SF3B1, U1, XPO1, DDX3X, RPS15) (Table 1) [9,11,12]. The gene discussed is NOTCH1; the disease is B-cell chronic lymphocytic leukemia.