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Gene mutations predict leukemia patient outcomes

Decoding the DNA of a woman who died of acute myeloid leukemia (AML) has led Washington University researchers to a gene that they found to be commonly altered in many patients who died quickly of the disease. The findings, if confirmed in larger studies, suggest that a diagnostic test for mutations in the gene could identify AML patients who need more aggressive treatment right from the start. The new discovery also provides a concrete target for developing improved therapies against AML, one of the most common adult leukemias.

Studying nearly 300 AML patients, the researchers found those with a particular mutation in the DNMT3A gene survived for an average of just over one year after their diagnosis, compared with nearly 3.5 years for those without the mutation. Notably, the investigators found the mutations in one-third of the patients whose prognosis would be unclear based on current diagnostic tests. These patients typically receive standard chemotherapy drugs as a first-line treatment.

“Based on what we found, if a patient has a DNMT3A mutation, it looks like you’re going to want to treat very aggressively, perhaps going straight to bone marrow transplantation or a more intensive chemotherapy regimen,” says senior author Richard Wilson, PhD, director of Washington University’s Genome Institute.

The study was conducted by a large team of scientists at the Genome Institute and the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. They are pioneers in using a comprehensive, genome-wide approach to unravel the genetic basis of cancer. By decoding the genome— all the DNA—of cancer patients and their tumor cells, they can find critical mutations at the root of the disease. Then, the researchers can look for those errors in other patients.
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