CLL Global Research Foundation

Nicholas Chiorazzi, M.D.
The Feinstein Institute for Medical Research

BIOLOGY

Characterization of the Proliferating Compartment in B-CLL Patients and in Healthy Aging Subjects

Grant awarded in 2006

Abstract:

Clonal proliferation and growth are key elements in the development and progression of cancer. Despite the apparent lack of an easily detectable proliferative compartment, B-cell type chronic lymphocytic leukemia (B-CLL) is not an exception to this rule. Indeed, recent data highlight this point. Using the non-radioactive stable isotope deuterium, administered to patients in the form of heavy water (2H2O), we recently determined that B-CLL cell birth and death occur at a substantially higher level than previously realized.

Several unanswered questions should now be addressed: What are the proliferating cells in B-CLL? Is there a normal circulating B-cell subset that has kinetic profiles similar to B-CLL cells? What is the scope of genetic changes that occur in a normal B-cell to transform them into B-CLL cells and to transform B-CLL cells into more dangerous clones? Finally, when a larger number of patients are studied, will there be a correlation between B-CLL cell kinetics and the serum, cellular, and molecular markers of outcome?

Having demonstrated the success of 2H2O labeling in defining the proliferative history of B-CLL cells, we expect that, by combining this approach with established techniques of immunofluorescence and cell isolation, we will identify and characterize the proliferating cells in this leukemia. We will then compare the kinetics of these cells with potential normal counterparts that are available in the blood. In these studies, we will be looking to define the development of new cytogenetic lesions that could presage changes in the clinical behavior of the leukemic clone. Furthermore, we intend to characterize those normal B-lymphocytes that eventually become B-CLL cells, especially those which are clonally expanded in normal individuals and, more so, in apparently healthy relatives of patients having B-CLL.