Jan. A. Burger, M.D., Ph.D. University of Texas MD Anderson Cancer Center

CLL-STROMA INTERACTION

Understanding and targeting the social network of CLL cells with their neighbors

Grant Awarded in 2008

Abstract:

In CLL, there is a fatal attraction between the leukemia cells and "feeder cells" that are present in lymph nodes and the bone marrow. These "feeders" (which also are called nurselike cells or stromal cells) provide CLL cells with nutrients and drug-resistance signals. Therefore, the main focus of our research program is to find out which molecules are important for this interaction between CLL and the "feeder cells," and to find novel drugs to interrupt this "food chain".

Our research has already identified two factors called CXCR4 and CXCR5 that make CLL cells move and stick to "feeder cells". We now are testing new drugs that blocks CXCR4, and are planning to bring these drugs into clinical trials in CLL patients in the near future.

However, once CLL cells stick to "feeder cells," CXCR4 is clearly not the only survival factor. Therefore, we will conduct studies to systematically analyze how CLL cells "talk" with "feeder cells". This will be done by a new technique called gene expression profiling. This technique allows us to determine which genes get turned on once CLL cells stick to the "feeder cells". Using this approach, we should be able to define new targets for therapy. These experiments will be conducted in collaboration with Dr. Rosenwald from Würzburg University in Germany, who is a pioneer in this field.

Moreover, we have established a standardized method to culture CLL cells with different types of "feeder cells". Previously, drugs for treatment of CLL were tested in the laboratory without any "feeder cells," not taking into account the drug resistance signals that CLL cells receive from the "feeder cells" in CLL patients. Establishing this new method will allow us to systematically analyze how well new drugs work, and to test drugs that interfere with the fatal attraction between CLL cells and "feeder cells".

Ultimately, this research will lead to innovative, targeted therapies for CLL patients, but with a paradigm shift: from targeting only the CLL cells towards targeting the CLL cells in the context of their complex social network.