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August 6, 2009

Researchers Find Gene Silenced Early in the Development of Chronic Lymphocytic Leukemia

  • A gene called FOXD3 is turned off early in the development of chronic lymphocytic leukemia (CLL), before clinical signs of the disease appear, according to a team of scientists. They thus suggest that epigenetic alterations could serve as markers for detecting CLL early and for monitoring its progression.

    The findings are published online in the Proceedings of the National Academy of Sciences in a paper titled “Epigenetic changes during disease progression in a murine model of human chronic lymphocytic leukemia.” 

    The study examined cancer cells from patients with CLL and from a strain of mice that develops characteristics of this disease. “Our data suggest that the silencing of FOXD3 might represent a very early gene involved in the initiation of CLL that we can potentially target for re-expression with specific drugs,” comments study leader, John C. Byrd, M.D., professor of internal medicine, director of the hematologic malignancies program at the Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute.

    The animal model, called the TCL1 transgenic mouse, was developed by Ohio State cancer researcher Carlo M. Croce, M.D., and a group of colleagues in 2002. An earlier study by Dr. Byrd’s laboratory showed that the disease in the mouse has many of the same molecular and genetic features as human CLL, responds to drugs used to treat the disease, and develops drug resistance as CLL patients often do. 

    “We know that human CLL involves the silencing of a number of genes, but we can look at human CLL only after patients develop the disease,” Dr. Byrd points out. “This mouse model now allows us to look at events leading up to the disease and perhaps identify markers for early disease detection and the testing of new therapies.”


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