Genetic studies have identified several lesions (abnormalities of TP53, MYC, CDKN2A, and IGH-mediated translocations) [11, 33, 34] associated with RT pathogenesis, and currently a number of genetic biomarkers (NOTCH1 mutation, IGHV4–39) are used to identify CLL patients at risk of RT. The gene discussed is NOTCH1; the disease is B-cell chronic lymphocytic leukemia.