Zeev Estrov, M.D. University of Texas MD Anderson Cancer Center

CLL-STROMA INTERACTION

Role of STAT3 in CLL

Update:

We studied the interaction between chronic lymphocytic leukemia (CLL) cells and their surrounding bone marrow. We found that CLL cells produce a hormone-like factor called vascular endothelial growth factor (VEGF). Previous studies showed that VEGF induces the growth of small blood vessels. Indeed, we found that the bone marrow of patients with CLL contains more small blood vessels than the bone marrow of healthy individuals. These findings suggest that by producing VEGF, CLL cells change the composition of their surrounding bone marrow.

We also found that CLL cells stick to bone marrow blood vessels including the small blood vessels whose growth was induced by VEGF. CLL cells bind to the cells that form the lining of the inner surface of blood vessels, termed vascular endothelial cells. Our experiments show that VEGF, as well as endothelaial cells, provide CLL cells with protection against cell death. In addition, we discovered that CLL cells express the receptor for VEGF on their surface and that when VEGF (including the VEGF that is produced by CLL cells) binds to this receptor, CLL cells are better protected from cell death. These data suggest that inhibitors of VEGF should be used as anti-CLL agents.