Peng Huang, M.D., Ph.D. University of Texas MD Anderson Cancer Center

NEW DRUGS

A Novel Therapeutic Strategy to Overcome CLL Drug Resistance Induced by Stromal Factors

Update:

The main purpose of this research project is to use a special cell culture system in which leukemia cells isolated from CLL patients are co-cultured with stromal cells of the bone marrow. This has allowed us to investigate the interactions between leukemia cells and the tissue microenvironment (stromal). The specific goals are to understand how stromal cells may protect leukemia cells and make them more resistant to chemotherapy and to test new drugs that can overcome such drug resistance.

During the first year of this research project, we have successfully accomplished the proposed studies in accordance with the original timetable and milestones. All proposed studies for the first year have been completed with significant new findings on the biochemical processes by which stromal cells promote CLL cell survival and drug resistance through an increased synthesis of an important molecule known as glutathione. Furthermore, we found an effective way to abolish this glutathione protection so that the leukemia cells become sensitive to drug treatment with standard agents such as fludarabine.

In addition, our study also led to an invention of novel drug-containing nanomolecules for potential use in CLL treatment, and a discovery of a small molecular weight compound that can selectively kill CLL cells in the presence of stromal cells. These new agents have high potential to improve the CLL treatment outcome, since they are effective in eliminating CLL cells in the stromal environment of the CLL patients.