The advent of specific culture protocols with the addition of mitogens, namely CD40 ligand (CD40L) or CpG-oligonucleotide DSP30 plus interleukin-2 (IL-2) allowed the performance of large cytogenetic studies that further highlighted the association between CK and inferior clinical outcome in CLL. This evidence concerns the gene CD40LG and B-cell chronic lymphocytic leukemia.