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

BIOLOGY

Effect of Microenvironment on Mcl-1 in CLL cells

Grant awarded in 2009

Abstract:

Programmed cell death, also known as apoptosis, maintains the optimal level of normal cells in the body. This process is regulated by proteins that are either prosurvival or proapoptotic. For chronic lymphocytic leukemia (CLL) cells, there is a survival advantage due to the presence of anti-apoptotic proteins. The first member of this family was identified as Bcl-2 protein. Another member is known as Mcl-1.

Several investigations have demonstrated that CLL cells express high levels of Mcl-1 protein which provides a survival advantage by blocking apoptosis and consequently increasing CLL lymphocytes in the body. In addition, microenvironment factors present in bone marrow stromal cells or in the lymph nodes, further increase levels of Mcl-1 in CLL lymphocytes. We hypothesize that the increase in Mcl-1 in CLL cells by the microenvironment happens through several pathways. Identification of these mechanisms will provide therapeutic options to disrupt them.

Based on our preliminary data, we propose to identify the mechanism by which Mcl-1 is increased in CLL cells when they are co-cultured with stroma cells. This will be achieved by determining transcription of Mcl-1 gene, synthesis of Mcl-1 protein, and changes on the protein to make it more stable.