We are interested in applying advances in cellular and molecular biology to improving therapy of B cell malignancies. One area of current focus is on mechanisms of action and resistance to monoclonal antibodies such as rituximab, and enhancement of antibody activity by down-regulating BCL2 function. This work led to a recent clinical trial of the antisense BCL2 oligonucleotide oblimersen + rituximab in relapsed B cell lymphoma. Another area of interest is mantle cell lymphoma, for which we have developed an animal model based on immune stimulation of older mice genetically susceptible to this lymphoma by being transgenic for cyclin D1 overexpression. We are involved in clinical trials for mantle cell lymphoma, including one using a cdk targeted agent to block the cyclin D1 pathway.