Varsha Gandhi, Ph.D. University of Texas MD Anderson Cancer Center

NEW DRUGS

Targeting anti-apoptotic proteins in CLL

Grant Awarded in 2008

Abstract:

CLL is an incurable disease representing the most common form of leukemia in North America. This disorder is characterized by a disrupted cell death pathway rather than increased rate of cell production. The CLL cell death pathway is disrupted because of a prominence of anti-apoptotic (anti-cell death) proteins belonging to Bcl-2 family proteins.

Recently, agents have been identified that target these anti-apoptotic proteins directly by binding to them. Such an action results in inhibition of these proteins leading to removal of survival advantage from the CLL cells. We plan to use three agents that target Bcl-2 family of anti-apoptotic proteins.

Our plan is to first identify the characteristics and functional role of anti-apoptotic family proteins in primary CLL cells and to investigate the mechanism by which anti-apoptotic protein antagonist(s) induce cell death. Second, we will test if microenvironment induces expression of Bcl-2 family proteins in CLL lymphocytes and protects these primary cells from Bcl-2 antagonist-induced cell death. Finally, we plan to evaluate mechanism-based combinations of established and experimental chemotherapeutic agents with Bcl-2 antagonist(s) in CLL lymphocytes.