BCL2/TRAF2DN transgenic mouse model represents a very interesting parallel and confirmation for the idea of two cooperating tumor suppressors at 13q14. Although BCL2 or TRAF2DN single transgenics do not develop CLL, TRAF2DN/BCL2 double transgenic mice over time developed B-cell leukemias of B220+CD5+ phenotype similar to CLL.[59] Since human 13q14 region contains two cooperating tumor suppressors, miR-15/16 and DLEU7, 13q14 deletions cause inactivation of both genes. MiR-15/16 inactivation causes a constitutive increase of Bcl2 expression, DLEU7 inactivation causes induction of TNF signaling through TRAFs. These two events cause the CLL phenotype closely resembling the oncogenic events in TRAF2DN/BCL2 transgenic mouse model (Figure 1) [20].
