NOTCH1 mutations have also recently been reported in approximately 10% of chronic lymphocytic leukemia and are typically PEST domain mutations in that disease. In CLL, NOTCH1 mutations and tend to be exlusive of SF3B1 mutations and possibly TP53 mutations, although some studies demonstrate that NOTCH1 mutations are associated with mutations of TP53. In CLL, the presence of NOTCH1 mutations has been associated with trisomy 12 and aggressive biologic features(CD38+, ZAP70+, unmutated IgH variable region) and adverse prognosis in some settings. The potential utility of therapeutic targeting of activating NOTCH1 mutations in these diseases remains to be elucidated.