While a great deal of progress has been made in treating some forms of leukemia, the long-term survival rate for leukemia patients has reached a plateau. This is largely a result of the fact that the current treatments are designed to kill the bulk of the tumor cells that are actively multiplying, but do not affect the small population of cancer stem cells that are dormant or sleeping. These rare stem cells are resistant to these drug treatments and contribute to the cancer's relapse when they do wake up and begin multiplying. Recent studies by the Müschen laboratory have shown that these sleeping leukemia cells produce high levels of BCL6, a factor that controls the production of many important genes involved in cell division. Müschen now proposes to use a novel drug which can stop BCL6 from functioning and also works cooperatively with standard leukemia treatments. These studies will test the importance of BCL6 in initiating leukemia and causing relapse, determine the frequency of BCL6-expressing stem cells in human leukemia samples, and conduct preliminary work with the new BCL6 inhibitory drug necessary for clinical trials. This work will provide important insight into the role of BCL6 in leukemia development, treatment, and resistance that could lead to a novel therapeutic strategy using a combination of drugs to target both active and dormant cells, thus reducing the chances of resistance.
Markus Müschen, M.D., director of the Leukemia Research Program at Childrens Hospital Los Angeles and the Leukemia and Lymphoma Program in the University of Southern California Norris Comprehensive Cancer Center; associate professor of pediatrics, biochemistry and molecular biology at the University of Southern California, Keck School of Medicine
Watch an interview with Dr. Müschen on YouTube:
Updated Mar. 22, 2010