Notch mutations have been shown in two studies to be the most frequent lesion, with Notch2 gain-of-function gene mutations in approximately 20-25% of all SMZL cases, causing impaired degradation of the NICD in a similar fashion to Notch1 mutations in MCL, CLL, and some forms of T-ALL [110, 111]. This evidence concerns the gene NOTCH2 and B-cell chronic lymphocytic leukemia.