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Researchers discover inherited mutation for leukemia

COLUMBUS , Ohio Researchers have discovered the first inherited gene mutation that increases a person's risk for chronic lymphocytic leukemia (CLL), one of the most common forms of the disease.

The study shows that the inherited mutation greatly reduces the gene's protective activity. Furthermore, a second kind of change occurs later that turns the gene off altogether, leading to leukemia. This latter alteration is a chemical change that is not inherited.

The findings could help identify people at risk for chronic leukemia, but they also may provide new insights into the process of natural cell death. They may even lead to new strategies for treating the disease.

The research is to be published in the June 1 issue of the journal Cell. It was led by researchers at the Ohio State University Comprehensive Cancer Center.

The mutation was found in a gene called DAPK1, which normally helps trigger the death of cells before they become cancerous. Researchers identified the mutation by testing a family in which the father, four sons, a grandson and a distant female relative developed this form of leukemia.

The chemical change is called DNA methylation. Healthy cells use this process to silence unneeded genes. But abnormal DNA methylation can turn off genes that control cell growth, and that lead to tumor growth.

"Our findings identify for the first time a gene that appears to be associated with hereditary CLL," says coauthor John C. Byrd, professor of internal medicine and a CLL specialist.

"They also show the importance of the gene in the pathogenesis of CLL, and direct us to target this gene with therapies that might re-activate it."

The findings also provide evidence that some genes might contribute to cancer even when they are not silenced entirely.

"This inherited change is remarkably subtle," says co-principal investigator Albert de la Chapelle, professor of molecula
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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University
31-May-2007


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