The frequency of genomic alterations affecting NOTCH1 signalling is rising over the CLL disease course culminating in the observation that besides TP53 loss, 8q gain and CDKN2A/B loss, NOTCH1 mutation is a hallmark genomic alteration associated with transformation of CLL into an aggressive lymphoma (Richter transformation). Here, TP53 is linked to B-cell chronic lymphocytic leukemia.