There are two main challenges to treating chronic lymphocytic leukemia (CLL): predicting the clinical course in a disease that shows many differences across patients, and overcoming the insensitivity of some patient tumors to chemotherapy. There is a need for improved understanding of how disease starts and progresses, which would lead to better predictive markers and potentially more effective (and non-toxic) therapies. Recent advances in genomic technologies provide a unique opportunity to find the genes and molecular circuits that make tumors grow in CLL. Wu is sequencing genes from tumor and normal cells from CLL patients. She is examining how genes are expressed in the same patient tumors using gene microarrays. Wu’s laboratory pioneered the use of silicon-coated nanowires as a method of delivering DNA, RNA to primary CLL and normal B cells, allowing her to genetically manipulate CLL cells for the first time in a high-throughput fashion. Her analysis thus far has identified genes important for CLL, and the nanowires have verified the importance of some of these genes in CLL tumor cells. This project enables Wu to find all the major genes and pathways that control CLL tumor formation. She will use a combination of sequencing technologies with statistical analyses to find the key genes that are important in creating tumors in CLL patients. In addition, she will determine which genes are good predictors of disease progression. Then, she will use nanowires to place the mutant genes from CLL tumors into normal B cells and see how they affect their behavior. This project will lead to an understanding of the basic reasons why CLL patients develop cancer. The information will help predict progression of disease and provide new strategies for therapy. Her approach can be extended to other tumors, especially leukemias and lymphomas.
Catherine J. Wu, M.D., is assistant professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute. She is staff physician at Brigham & Women’s Hospital and Dana-Farber Cancer Institute.
Updated: April 4, 2011