Indeed, consistent clinical outcomes have been reported for patients assigned to the same subset (60–62), likely linked to consistent biological profiles: these pertain, amongst others, to distinctive gene expression, cytogenetic aberrations, BcR structure and signalling capacity, epigenetic modifications and antigenic reactivity profiles (63–71) that are also distinct between subsets but also from non-subset cases even of the same mutational category (i.e. U-CLL or M-CLL). This evidence concerns the gene BCR and B-cell chronic lymphocytic leukemia.