U-CLL cases express unmutated immunoglobulin heavy variable chains (IGHV) and have a worse prognosis compared to M-CLL cases that originate from B cells that have undergone the germinal center reaction and express mutated IGHV. The B-cell receptor (BCR) is a major driver of disease progression [15] in both subsets of CLL and a classifier in calculating disease risk [18]. This evidence concerns the gene BCR and B-cell chronic lymphocytic leukemia.