At least 2 percent of people over age 40 and 5 percent of people over 70 have mutations linked to leukemia and lymphoma in their blood cells, according to new research at Washington University School of Medicine in St. Louis.
Mutations in the body's cells randomly accumulate as part of the aging process, and most are harmless. For some people, genetic changes in blood cells can develop in genes that play roles in initiating leukemia and lymphoma even though such people don't have the blood cancers, the scientists report Oct. 19 in Nature Medicine.
Li Ding, PhD, and colleagues at Washington University's Genome Institute found that many older people have mutations linked to leukemia and lymphoma in their blood cells.
Credit: Washington University in St. Louis
The findings, based on blood samples from nearly 3,000 patients, don't mean that people with these genetic mutations are destined to develop a blood cancer. In fact, the vast majority of them won't as the incidence of blood cancers such as leukemia or lymphoma is less than 0.1 percent among the elderly.
"But it's quite striking how many people over age 70 have these mutations," said senior author Li Ding, PhD, of The Genome Institute at Washington University. "The power of this study lies in the large number of people we screened. We don't yet know whether having one of these mutations causes a higher than normal risk of developing blood cancers. More research would be required to better understand that risk."
The researchers analyzed blood samples from people enrolled in The Cancer Genome Atlas project, a massive endeavor funded by the National Cancer Institute and the National Human Genome Research Institute at the National Institutes of Health (NIH). The effort involves cataloguing the genetic errors involved in more than 20 types of cancers.
The patients whose blood was analyzed for the current study had been diagnosed with cancer but were not known to have leukemia, lymphoma or a blood disease. They ranged in age from 10 to 90 at the time of diagnosis and had donated blood and tumor samples before starting cancer treatment. Therefore, any mutations identified by the researchers would not have been associated with chemotherapy or radiation therapy, which can damage cells' DNA.
The researchers, including Genome Institute scientists Mingchao Xie, Charles Lu, PhD, and Jiayin Wang, PhD, zeroed in on mutations that were present in the blood but not in tumor samples from the same patients. Such genetic changes in the blood would be associated with changes in stem cells that develop into blood cells, but not to the same patient's cancer.
They looked closely at 556 known cancer genes. In 341 patients ages 40-49, fewer than 1 percent had mutations in 19 leukemia- or lymphoma-related genes. But among 475 people ages 70-79, over 5 percent did. And over 6 percent of the 132 people ages 80-89 had mutations in these genes.
The researchers noted that nine of the 19 genes were mutated repeatedly, an indicator that the changes drive or initiate the expansion of blood cells with these mutations.
This expansion of cells is clearly not leukemia or lymphoma, the researchers said. It may be a precursor to blood cancers in a small subset of patients, but the study was not designed to predict the future risk of developing these diseases.
The current study likely underestimates the percentage of people with mutations in leukemia and lymphoma genes because the researchers only were able to identify small mutations, not large structural variations or the insertions and deletions of chunks of genetic material.
Still, it would be premature for people to undergo genetic testing to see if they have mutations linked to leukemia and lymphoma as a means to predict their risk of blood cancers.
"We would not want anyone to think they should be screened for these mutations to understand their risk of leukemia or lymphoma," said co-author and leukemia scientist Timothy Ley, MD, the Lewis T. and Rosalind B. Apple Professor of Oncology. "The ability to understand how mutations in these genes increase a person's risk of blood cancers is a long way off, and genetic testing would be of no benefit at this time."
If the researchers repeated the study in tens of thousands of patients and tracked the development of mutations over time, they could more accurately identify the risk of individual mutations or combinations of mutations for the development of leukemia and lymphoma. Such a study is intriguing to contemplate but would take years to complete and require considerable financial resources, Ding said.
The research is funded by the National Cancer Institute and the National Human Genome Research Institute at the National Institutes of Health (NIH). Grant numbers R01CA180006, PO1CA101937, U54HG003079 and U01HG006517.
Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC, McMichael JF, Schmidt HK, Yellapantula V, Miller CA, Ozenberger BA, Welch JS, Link DC, Walter MJ, Mardis ER, Dipersio JF, Chen F, Wilson RK, Ley, TJ and Ding L. Age-related cancer mutations associated with clonal hematopoetic expansion. Nature Medicine, advance online publication Oct. 19. 2014.
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Caroline Arbanas | Eurek Alert!
Correct connections are crucial
26.06.2017 | Charité - Universitätsmedizin Berlin
One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
27.06.2017 | Power and Electrical Engineering
27.06.2017 | Information Technology
27.06.2017 | Physics and Astronomy