To investigate the origin of these mutations, the researchers isolated blood stem cells from healthy people of different ages. The youngest were newborns, and the oldest was in his 70s.
Every person has about 10,000 blood stem cells in their bone marrow, and the researchers found that each stem cell acquires about 10 mutations over the course of a year. By age 50, a person has accumulated nearly 500 mutations in every blood stem cell.
"Mutations are known to develop in cells as we age, but no one had any idea how many mutations occur in blood stem cells and how frequently they develop," Link says. "These random, background mutations occur during cell division and are unrelated to cancer. Our DNA can tolerate a huge number of these hits without any negative consequences. But if a cancer-initiating event occurs in one of these stem cells, it captures the genetic history of that cell, including the earlier mutations, and drives leukemia to develop."
As part of the study, the researchers sequenced the genomes of 24 patients with AML and compared the mutations in their leukemia cells to those that occurred in the blood stem cells of the healthy individuals. The scientists were surprised to see that the total number of mutations varied by age, not by whether a patient had leukemia. Thus, a healthy person in his 40s had just about the same number of mutations in his blood stem cells as a leukemia patient of the same age had in his cancer cells.
The study's results help to explain why leukemia occurs more frequently as people age.
"AML is relatively uncommon until about age 60," says co-first author John Welch, MD, PhD, assistant professor of medicine. "It is the persistent, random accumulation of mutations in blood stem cells that contributes to the risk of the disease
|Contact: Caroline Arbanas|
Washington University School of Medicine