New genetic and epigenetic alterations in the genome, discovered by scientists at The Cancer Genome Atlas Research Network, offer promising disease markers for acute myeloid leukemia--a finding that may have narrowed the search for drug targets.
Acute myeloid leukemia, or AML, is a deadly type of cancer that starts inside the bone marrow and grows from cells that are supposed to turn into disease-fighting white blood cells in a healthy person.
The researchers found that, compared to other types of cancer that affect adults, AML has relatively few pronounced mutations. But the disease is markedly influenced by mutations in genes that cause epigenetic changes--chemical changes to the genome that do involve a change in the DNA nucleotide sequence. The research appeared online May 1 in the New England Journal of Medicine.
"These findings have probably identified every pathway in which a modification--and perhaps new drugs--might be beneficial," study co-leader Richard Wilson, Ph.D., director of Washington University's Genome Institute, said in a statement. "They also further refine our understanding of the importance of individual mutations for disease classification and prognostication, and will help us build better disease models."
In AML patients, undeveloped white blood cells fail to mature and end up building up in bone marrow. The bad cells--now leukemia cells--hinder the production of healthy blood cells, which can cause anemia, abnormal bleeding and infections, and, if untreated, death. Currently, only a few reliable biomarkers have been identified to help make treatment decisions for most patients at intermediate risk for AML, according to a National Institutes of Health statement.
Analyzing the genomes of tumor specimens from 200 adult cases of AML, researchers estimated that they were able to identify nearly all the mutations that occur in at least 5% of AML patients. They found that AML genomes had few mutations--on average 13--compared to hundreds of mutated genes found in breast, lung or pancreatic cancer.
Across the 200 samples, scientists found more than 1,600 genes that were mutated at least once, including tumor suppressor genes, signaling genes and epigenetic modifiers--which occurred most frequently in the study.
The research may help identify more effective drug targets, tailor treatments to individuals and better predict the severity of AML in patients.
- here's the NIH press release