Alteration in DAPK1, which normally protects cells, reduces the gene’s expression increasing cancer risk.

Researchers at Ohio State University Comprehensive Cancer Center discovered an inherited gene mutation in DAPK1, which normally helps trigger the death of cells before they become cancerous, 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 DAPK1’s protective activity. Furthermore, it found that DNA methylation of the gene occurs later, which turns the gene off altogether, leading to leukemia. This latter alteration is a chemical change that is not inherited.

“Our findings identify for the first time a gene that appears to be associated with hereditary CLL,” says co-author John C. Byrd, M.D., professor of internal medicine. “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.”

“This inherited change is remarkably subtle,” says co-principal investigator Albert de la Chapelle, M.D., Ph.D., professor of molecular virology, immunology, and medical genetics. “It does not shut down the gene, but just lowers its expression somewhat.

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