Most CLL-related NOTCH1 mutations are located in exon 34 and the 3’ untranslated region (UTR), resulting in truncation of NOTCH1 by deletion of the C-terminal PEST (proline, glutamine, serine and threonine-rich) domain, which regulates degradation of active NOTCH1 [12, 13]. Here, NOTCH1 is linked to B-cell chronic lymphocytic leukemia.