While NOTCH1 pathway alterations play a critical role in CLL biology, mutations in NOTCH2 are prevalent in SMZL, affecting 20% of cases; however, like NOTCH1 mutations in CLL, the majority of NOTCH2 mutations in SMZL affect the C-terminal region PEST domain of the NOTCH2 receptor [7,11]. Here, NOTCH2 is linked to B-cell chronic lymphocytic leukemia.