In particular, NOTCH1 seems essential to steer differentiation of lymphoid progenitors toward a T-cell phenotype [35] whereas NOTCH2 seems required for marginal zone B differentiation [40,41]; however, the role of NOTCH1 is also evident in mature B cells and is significantly expressed in both naïve and memory B cells [18], which are the putative cells of origin of CLL [42]. The gene discussed is NOTCH2; the disease is B-cell chronic lymphocytic leukemia.