A number of recurrent driver gene mutations was detected in CLL by next generation sequencing (NGS) and excellent reviews highlighted that, while the vast majority of them recur across patients at a low frequency, mutations of TP53, ATM, NOTCH1, and SF3B1 can be found in >5% of treatment-naïve patients and may predict for an inferior prognosis [48, 64–65]. This evidence concerns the gene NOTCH1 and B-cell chronic lymphocytic leukemia.