Methylation marker tags leukemia outcomes

Chronic lymphocytic leukemia (CLL) is one of the most common forms of leukemia--in the U.S. around 16,000 people will develop CLL this year and 4,600 people will die. In some people, the disease will stay dormant for years and need no treatment; in others it will move quickly and rapid treatment is vital. A biomarker spotted by researchers at the Ohio State University Comprehensive Cancer Center (OSUCCC) could help doctors pick out those patients who will need chemotherapy straight away and who can be spared needless and toxic treatment.

Increased expression of the gene ZAP-70 predicts a poor outcome for people with CLL, but there are issues with the existing tests, which rely on levels of the ZAP-70 protein and mutations in another gene, "but these assays are expensive and difficult to perform," says co-author and researcher Dr. David Lucas, research assistant professor and CLL specialist at the OSUCCC.

This means that doctors have to rely on observing patients before deciding a course of treatment. However, an epigenetic change (a change to the DNA that doesn't affect its sequence) to the gene could make a test more accessible. The researchers looked at the level of methylation on the gene in 247 people with CLL and found differences in a small area of the gene. Healthy cells are fully methylated, and in people with a slower progressing from of CLL there are higher levels of methylation, but total loss of the methyl groups at a specific point on the gene predicts aggressive disease, suggesting that treatment should start immediately. The results are published in the Journal of Clinical Oncology.

"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 Dr. John Byrd, a CLL specialist and professor of medicine, medicinal chemistry and veterinary biosciences at the OSUCCC.

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