Although the individual role of each of these genes in the pathogenesis and outcomes of CLL is currently being investigated, there is convincing data to show that CLL patients who harbor NOTCH1 mutation (mostly occurring in patients with trisomy 12), SF3B1 mutation (mostly occurring in patients with del13q14), and those with TP53 mutation experience a shorter time to first therapy, progression-free survival (PFS), and OS20–25. The gene discussed is TP53; the disease is B-cell chronic lymphocytic leukemia.