NF-kB is a downstream target of TRAFs (Figure 1). Hence, it is possible that activation of NF-kB plays a role in the pathogenesis of CLL. Thus, a study described another mouse model for CLL suggesting the involvement of NF-kB. The study reported a transgenic line expressing APRIL (a proliferation-inducing ligand) under control of the T-cell specific lck promoter [22]. APRIL is a secreted protein, thus its over-expression in T-cells caused elevated APRIL levels in serum. In fact, APRIL works systemically in these transgenic mice affecting proliferation and survival of B-cells [22]. These expanded mature B-cells revealed significant increase in survival in vitro in comparison to normal B-lymphocytes [21, 22]. The expansion of B220+CD5+ cells was observed in ~40% of transgenic animals in contrast with other described CLL mouse models where the penetrance was appoximately 100%. Generally, APRIL transgenics showed much milder phenotype than TCL1 or TRAF2DN/BCL2 transgenic animals. APRIL mice showed only mild expansion of splenic B-cells, they did not develop high blood white cells count and did not die prematurely from leukemia or lymphoma. Hence, it is possible that
