As mentioned previously in this review, a link between genomic abnormalities and high expression levels of Bcl2 in the majority of CLL patients was established by the discovery of the role of miR-15a/16-1 in the disease. Thus, deregulation of BCL2 is most likely a major contributor to the pathogenesis of CLL, specifically the indolent form of CLL that is often accompanied by 13q14 deletions. A study by Dr. Reed’s laboratory provided an important evidence in favor of this hypothesis [59]. The study was based on two previous models, a mouse over-expressing Bcl2 in the lymphoid system [60] and a transgenic line over-expressing an isoform of TRAF2 in murine B- and T-cells [61]. TNF receptor associated factor 2 (TRAF2) belongs to a family of adaptor proteins that bind to TNF receptor family members and mediate the activation of NF-kB and JNK by the tumor necrosis factor proteins (Fig. 2) [62]. Increase in lymphocyte proliferation and survival is led by TNF-mediated signaling [24]. TRAF2 transgenic mice over-expressed TRAF2 mutant, lacking the N-terminal RING and zinc finger domains located at the N- terminal
