Guillermo Garcia-Manero, M.D. University of Texas MD Anderson Cancer Center

GENETICS

Epigenetic and therapeutic profiling of chronic lymphocytic leukemia

Update:

Our project focuses on the study of epigenetic alterations in CLL. In particular, we analyzed aberrant DNA methylation patterns. DNA methylation is a biochemical modification of DNA that results in gene silencing. If this occurs in tumor suppressor genes, it may contribute to the development of CLL.

We have developed a new strategy to detect previously unknown genes methylated in CLL. This strategy consists of the use of a new promoter microarray completed with a technique known as MCA. We have identified in excess of 200 new potential tumor suppressor genes in CLL, and we have validated approximately 30 of them (both at the DNA and gene expression levels). These genes clustered more frequently on chromosome 17 (a poor prognostic region in CLL), and can be grouped into 20 molecular networks. Some of these genes also have prognostic value. Next, we plan to study these genes in the setting of FCR (fludarabine, cyclophosphamide & rituximab) therapy in collaboration with Dr. Wierda.