SUMMARY
The laboratory research of Neil E. Kay, M.D., is focused on B-chronic lymphocytic leukemia (CLL). 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, it proves to be an ideal tumor model for a variety of in vitro studies. To support the laboratory studies described below, Dr. Kay and his colleagues have established an extensive CLL tissue bank and clinical database that is a rich, nationally recognized resource for CLL studies.
Dr. Kay's work involves close collaboration with several other talented scientists at Mayo Clinic, including Diane F. Jelinek, Ph.D., in the Department of Immunology; Curtis A. Hanson, M.D., and Daniel L. Van Dyke, Ph.D., in the Department of Laboratory Medicine and Pathology; James R. Cerhan, M.D., Ph.D., in the Division of Epidemiology; and Susan L. Slager, Ph.D., in the Division of Biomedical Statistics and Informatics.
This collaboration has provided for unique studies in CLL that now include extramurally funded studies in CLL B-cell signaling, detailed epidemiological studies of CLL and genome-wide analysis of familial CLL patients (CLL families with two or more CLL patients).
Dr. Kay is also very involved in the design and implementation of CLL clinical trials for previously untreated and treated CLL patients that incorporate the latest novel drugs alone or in combinations. These trials are conducted within the national cooperative group system of the United States.
Focus areas
Microenvironment. Dr. Kay's studies on the microenvironment are based on the fact that resistance to spontaneous apoptosis and drug resistance is a dominant feature of leukemic B-cell interaction with stromal cells. Therefore, further understanding of the mechanism(s) for the apoptosis resistance with this leukemic B cell-stromal cell interaction is crucial to discovering novel therapies for this disease. These mechanisms are complex, but likely to provide unique strategies for CLL therapy.
For example, Dr. Kay and his team have found that angiogenic factors, including vascular endothelial factor and basic fibroblast growth factor, can 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 be related to the aggressiveness of this disease.
B-cell biology. Dr. Kay has focused in recent years on more extensive genetic analysis of the leukemic B cell. For this analysis, he has used a variety of approaches, including fluroscent in situ hybridization (FISH), comparative genomic hybridization, microRNA and messenger RNA analysis, and most recently whole-genome sequence studies. These latter tools have been insightful in allowing Dr. Kay and his colleagues to uncover and publish key genetic aspects of CLL clones that most prominently include evidence for definition of CLL risk groups in relation to disease course and for clonal evolution in this disease.
The latter feature has uncovered novel patterns of clonal architecture not previously appreciated, and Dr. Kay believes it will help more accurately determine the clinical course for a given patient. This work, which uses whole-genome sequencing, can also have the potential to identify drug-resistant clones and help develop targeted therapy for CLL patients.
Significance to patient care
Dr. Kay and his colleagues have accumulated a large database of both clinical information and tissue samples (such as blood and marrow) from CLL patients. The latter effort is able to collect valuable information on critical biologic and prognostic features of CLL patients that can be correlated with their clinical outcomes. The work that stems from this database provides information on strategies for unique therapies.
This project was started almost from the outset of Dr. Kay's tenure at Mayo Clinic, which began 12 years ago. It continues to be a rich resource for the clinical, translational and basic biologic research of Dr. Kay and his colleagues. Their clinical trials portfolio is extensive in that they have approaches that try to encompass all cohorts of CLL patients, from those with early-stage disease to those with more advanced stages of disease.
Professional highlights
- Member, Leukemia Steering Committee, National Cancer Institute
- Chairman, CLL Steering Committee, National Cancer Institute
- Member, Leukemia Core Committee, Eastern Cooperative Oncology Group
- Member, External Advisory Group (CLL), MD Anderson Cancer Center
- Section Editor, Leukemia