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Research Update

DNA Arrays Diagnose, Predict Survival for Sézary Syndrome

Louise C. Showe, Ph.D., of the Wistar Institute in Philadelphia, Pennsylvania, has recently reported the use of DNA array technology to identify important genes involved in Sézary syndrome. DNA arrays provide scientists with the ability to assess the activity of thousands of different genes and determine which genes are turned on or off in any particular tissue studied. Dr. Showe utilized customized DNA arrays to analyze 4,500 genes and identified 385 genes that were either overactive or underactive in blood samples taken from the 45 Sézary syndrome patients, as compared to 20 normal controls.

Studying the activity of only eight of the 385 genes permitted investigators to accurately diagnose Sézary syndrome in patients with as low as five percent abnormal (Sézary) cells circulating in their blood. A panel of ten genes appeared to provide prognostic information, as it predicted a subset of patients that died of their disease within six months, regardless of their tumor burden. And one gene was seen to occur in about 70 percent of the Sézary patients but never in the controls, making it a highly specific marker for the malignant cells.

The research project was a collaborative effort between Dr. Showe and cutaneous T-cell lymphoma (CTCL) investigators Dr. Eric C. Vonderheid of Johns Hopkins University Medical Center and Dr. Alain H. Rook of the University of Pennsylvania Medical Center. Their work is reported in the June 2 issue of the Journal of Experimental Medicine and was supported by a research grant from the National Institutes of Health (NIH). With continued NIH funding, Dr. Showe plans to extend her collaborative work and study skin samples from patients with CTCL.

This research builds a foundation to identify genetic markers that will more accurately diagnose and predict the course of CTCL that, in the future, may help guide clinicians weighing treatment options for their patients. In addition, each of the genes identified may be a potential target for drug development, greatly expanding the field of possibility for future treatments.