Most CLL mutations which affect NOTCH1 are frameshift or nonsense events which are clustered within exon 34 (including a highly recurrent c.7544_7545delCT deletion) and are selected to disrupt the PEST domain of the protein (Fabbri et al., 2011; Rossi et al., 2012; Sportoletti et al., 2010). Here, NOTCH1 is linked to B-cell chronic lymphocytic leukemia.