Recent deep sequencing studies have identified acquired mutations that result in deletion of the C-terminal PEST domain in 10-15% of human chronic lymphocytic leukemia (CLL) [22], [23], a type of Notch1 mutation originally identified in human T-cell acute lymphoblastic leukemia (T-ALL) [24] that stabilizes ICN1 and enhances the transactivation of target genes in leukemia cells. The gene discussed is NOTCH1; the disease is B-cell chronic lymphocytic leukemia.