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Marker Distinguishes Aggressive Form of Chronic Leukemia

John ByrdResearchers have identified a prognostic marker in the most common form of chronic leukemia that can help distinguish patients who should start treatment quickly from those who can safely delay treatment, perhaps for years.

The study, led by researchers at the OSUCCC – James, focused on chronic lymphocytic leukemia (CLL). Examining a gene called ZAP-70 in CLL cells for a chemical change called methylation, they found that, when this gene in leukemia cells is methylated, patients are likely to have the slow-progressing form of CLL. When the ZAP-70 gene is unmethylated, patients are likely to have aggressive disease and should consider immediate treatment.

Currently, doctors must simply observe newly diagnosed patients to determine which type of CLL they have. This can delay the start of treatment in patients with aggressive disease, or it can lead to treating patients who don’t yet require it.

“This study demonstrates that ZAP-70 methylation status is a highly predictive, reproducible biomarker of poor prognosis in this disease, and a clinically useful prognostic test for CLL,” says principal investigator John C. Byrd, MD, a CLL specialist who directs the Division of Hematology at Ohio State.

The presence of mutations in a gene called IGVH and the amount of protein produced by the ZAP-70 gene in CLL cells are sometimes used to predict prognosis and response to treatment in people with this disease, “but these assays are expensive and difficult to perform,” says study co-author and researcher David Lucas, PhD.

“In all cells, some areas of DNA undergo methylation, which controls how that DNA is used,” Lucas says. “In cancer cells, the pattern of DNA methylation is often different from that of healthy cells, and this influences how much protein is produced by ZAP-70 and other genes.”

Published in the Journal of Clinical Oncology.

Visit the OSUCCC – James CLL Experimental Therapeutics Laboratory at http://cll.osu.edu.

To refer a patient, please call The James Line New Patient Referral Center toll free: 1-800-293-5066.

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