The presence and relevance of a functional connection between the BCR and NOTCH1 pathways in CLL is also supported by the lower redistribution of lymphocytosis and lower nodal shrinkage of NOTCH1-mutated CLL during ibrutinib treatment [232], and the peculiar association of NOTCH1 mutations with a specific stereotyped configuration of the BCR (IGHV4-39/IGKV1 (D)-39) defined as subset 8, which is characterized by robust BCR signaling and exhibits the highest risk for Richter transformation [233]. This evidence concerns the gene NOTCH1 and B-cell chronic lymphocytic leukemia.