Transgenic models of lymphoid neoplasia and development of a pan-hematopoietic vector

The pathways to lymphoid neoplasia have been explored in a number of transg enic models. Because B lymphoid malignancies often involve translocation of an oncogene (e.g, myc, bcl-2, cyclin D1) to an immunoglobulin locus, resul ting in its deregulated expression, the consequences of oncogene overexpres sion in lymphocytes can be evaluated with transgenes driven by an immunoglo bulin regulatory element, such as an enhancer from the IgH locus. Mice bear ing such transgenes have provided insight into the preneoplastic state, inc luding alterations in the control of cellular proliferation, differentiatio n or apoptosis. They have also allowed studies on oncogene cooperation in,t iro and the modulating effect of genetic background. Briefly reviewed here are the models studied in the authors' Laboratories. Mice bearing myc and b cl-2 transgenes have received most attention but others studied include abl , ras, cyclin D1 and bmi-1 oncogenes. Also discussed is a new transgenic ve ctor that should facilitate transgenic approaches to non-lymphoid leukemias , The vector bears elements from the promoter region of the vav gene, which is expressed almost exclusively in hematopoietic cells. It has proven capa ble of driving transgene expression throughout the hematopoietic compartmen t, including progenitor cells and their precursors. This novel vector shoul d aid studies on many aspects of hematopoiesis, including the modeling of l eukemogenesis.