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 of the molecule (TRAF2DN), which mimics TRAF1 [21, 61]. The mice developed splenomegaly, lympho-adenopathy and a higher number of B-cells but failed to develop a clear blood neoplasia. BCL2 transgenics were generated by using a construct that mimics t(14;18) translocation juxtaposing BCL2 oncogene with the immunoglobulin heavy-chain locus at 14q32 observed in human follicular lymphomas. These mice did not develop any malignant phenotype, but displayed polyclonal expansions of B-cells and a more pronounced in vitro B-cell survival [21, 60]. Contrary to the single transgenic animals, TRAF2DN/BCL2 double transgenics developed severe splenomegaly, and most rodents developed a B-cell leukemia similar to CLL with B-cell blood count as high as 40 times normal [59]. The mice died prematurely at 6–14 months of age, though Bcl2 or TRAF2DN single transgenics had a regular lifespan. As in the case of the TCL1 transgenic mice, malignant cells were B220+CD5+, with a small number of animals having B-cell expansions of a different subtype. In conclusion, it
