Interestingly, mutations in NOTCH1 and SF3B1 are also traced to multipotent hematopoietic stem/progenitor cells in some CLL cases, indicating that the acquisition of these mutations is the primary transformation event that most likely provides survival advantage for these transformed progenitors, which in turn acquire further disease-modifying mutations along the lymphoid differentiation and maturation process [33,34]. Here, NOTCH1 is linked to B-cell chronic lymphocytic leukemia.