Using Heavy Hydrogen to Answer Some Basic CLL Questions

[Guest guest]

[These are questions that have been in my mind for years. I'm glad

someone is examining them. Hope to have results soon.]

" Characterization of the Proliferating Compartment in B-CLL Patients

and in Healthy Aging Subjects "

Chiorazzi, M.D.

North Shore-Long Island Jewish Research Institute

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.