Mutations In Single Gene Predict Poor Outcomes In Adult Leukemia
Decoding the DNA of a woman who died of acute myeloid leukemia (AML) has led researchers at Washington University School of Medicine in St. Louis 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, a fast-moving blood cancer that kills 9,000 Americans annually.
Studying nearly 300 AML patients, the researchers found those with a mutation in the DNA methyltransferase 3A gene, or DNMT3A, survived for a median of just over one year after their diagnosis, compared with nearly 3.5 years for those without a mutation. The research is published online Nov. 10 in the New England Journal of Medicine.
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 go straight to bone marrow transplantation or a more intensive chemotherapy regimen,” says senior author Richard K. Wilson, PhD, director of Washington University’s Genome Center and professor of genetics and of molecular microbiology.
In an accompanying editorial, Kevin Shannon, MD, of the University of California at San Francisco, writes that the Washington University research “underscores the power of whole-genome sequencing studies to uncover new molecular lesions in cancer.”
The study was conducted by a large team of scientists at The Genome Center and the 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.
The new research dovetails with the work that Washington University genome scientists are engaged in as part of The Cancer Genome Atlas, a joint project of the National Cancer Institute and National Human Genome Research Institute to unravel the genetic basis of more than 20 different types of cancer.
“This discovery is a clear example of the power of comprehensive analysis of cancer genomes,” says Francis Collins, MD, PhD, director of the National Institutes of Health. “By using high-throughput DNA sequencing, researchers will be able to discover all of the common genetic changes that contribute to cancer. With that knowledge, a growing list of targeted treatments will be developed, based on a firm biological understanding of the disease.”