New Research May Lead To More Appropriate Leukemia Treatment Options

Researchers at Washington University School of Medicine in St. Louis have found a commonly altered gene among women who died quickly of acute myeloid leukemia (AML). These findings could lead to diagnostic tests to identify faster-progressing forms of the disease and more aggressive treatment. According to Richard K. Wilson, PhD, director of Washington University’s Genome Center, “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.”

AML is a blood cancer found in the bone marrow that spreads quickly inside its host and leads to the death of approximately 9,000 Americans each year. The average life expectancy after diagnosis of AML is three and a half years. The average life after a diagnosis among those with a mutation of the DNA methyltransferase 3A gene (DNMT3A) is little more than a year. According to hematologist Timothy Ley, “DNMT3A mutations appear to be relevant for how the disease develops or progresses because these mutations have such huge a impact on outcome.”

DNMT3A assists with blood-forming cells in utero and throughout a person’s life. “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.”

The Genome Center and the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine where the study took place are known for their comprehensive, genome-wide approach to cancer research. They study all of the DNA, or the genome, to find subtle mutations associated with the disease. “This work represents the culmination of years of collaborative research that has focused on cataloging the mutations involved in AML,” says co-author John DiPersio, MD, PhD, the Virginia E. and Sam J. Goldman Professor of Medicine, chief of the Division of Oncology and deputy director of the Siteman Cancer Center. “This research provides a pathway and a foundation for doing the same in all other malignancies, which could potentially lead to better diagnostic tests and more effective, targeted therapies.”

Researchers will now look to how the mutation occurs.

Working within the larger scope of The Cancer Genome Atlas Project, involving both the National Cancer Institute and National Human Genome Research Institute, scientists research more than 20 different types of cancer.

Findings indicate that more than half of all AML patients are classified as intermediate risk. In the study of DNMT3a, researchers found that 34 percent of intermediate patients had the mutation. And of those classified intermediate risk, those receiving bone marrow transplants lived longer than those receiving just chemotherapy.

Researchers caution that the study was based on a small sample size. However, if the investigations of other researchers validate the findings, scientists could develop a diagnostic test to determine more successful courses of treatment for those with the mutation.

According to Ley, “We have not had a reliable way to predict which of these patients will respond to the standard treatment. In the cases we studied, mutations in the DNMT3A gene trump everything else we’ve found so far to predict adverse outcomes in intermediate-risk AML.”