B-chronic lymphocytic leukemia is the focus of our laboratory work. This most common and still incurable leukemia is not fully understood in terms of both its clinical and biologic heterogeneity. However, because it is both a frequently diagnosed leukemia and provides ready access to leukemic cells, this proves to be an ideal tumor model for a variety of in vitro studies.

To that end, our laboratory focuses on two major aspects of B-chronic lymphocytic leukemia B-cell biology, apoptosis and angiogenesis. Our studies in apoptosis are based on the fact that resistance to apoptosis characterizes a dominant feature of this leukemic B-cell. We also believe that this feature determines drug resistance in these patients. Therefore further understanding of the mechanism(s) for the apoptosis resistance is crucial in discovery of novel therapies for this disease. In addition, we are actively studying the role of angiogenic factors because these factors likely promote both the survival of the CLL B-cell and may have potential involvement in the growth of blood vessels in bone marrow and lymph nodes in this disease. This latter feature may relate to the aggressiveness of this disease.

Some recent observations in our laboratory have determined that CLL B-cells produce and secrete the cytokine Interleukin-4. In addition, we have determined that CLL B-cells possess membrane receptors for IL-4 which therefore provides an autocrine pathway for these leukemic cells. Importantly, IL-4 is a cytokine which increases CLL B-cell resistance to apoptosis, thereby providing one explanation for the resistance to apoptosis of these B-cells. We are conducting further analysis of the exact mechanism by which the IL-4 autocrine pathway promotes resistance to apoptosis in leukemic CLL B-cells. In angiogenesis we now know that there is evidence for both abnormal angiogenesis in the marrow and nodes of B-CLL patients.Importantly we have also found evidence for an autocrine pathway based on VEGF that impacts significantly on the level of both spontaneous and drug induced apoptosis in CLL B cells.

Currently our work involves close collaboration with several other scientists here at Mayo including Dr. Diane Jelinek in Department of Immunology, Drs. Hanson and Dewald in Hematopathology, Dr. Jim Cerhan in the Division of Epidemiology, and Dr. Susan Geyer in the Division of Biostatistics.