In CLL, both signaling pathways seem to be activated by microenvironment-related molecules such as CD40L for the canonical pathway and BAFF or APRIL for both, the canonical and non-canonical pathway (Fig. 1) (Furman et al., 2000; Endo et al., 2007; Ferrer et al., 2014). The gene discussed is CD40LG; the disease is B-cell chronic lymphocytic leukemia.