Hundreds of mutations exist in leukemia cells at the time of diagnosis, but nearly all occur randomly as a part of normal aging and are not related to cancer, new research shows.
Scientists at Washington University School of Medicine in St. Louis have found that even in healthy people, stem cells in the blood routinely accumulate new mutations over the course of a person's lifetime. And their research shows that in many cases only two or three additional genetic changes are required to transform a normal blood cell already dotted with mutations into acute myeloid leukemia (AML).
The research is published July 20 in the journal Cell.
"Now we have a very accurate picture of how acute leukemia develops," says senior author Richard K. Wilson, PhD, director of The Genome Institute at Washington University. "It's not hundreds of mutations that are important but only a few in each patient that push a normal cell to become a cancer cell. Finding these mutations will be important for identifying targeted therapies that can knock down a patient's cancer."
The study is the first to investigate how often mutations typically develop in healthy stem cells in the blood. These immature cells in the bone marrow give rise to all the blood cells in the body.
AML is a blood cancer that develops when too many immature blood cells crowd out the healthy cells. In recent years, Washington University researchers at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine have sequenced the genomes of 200 patients with AML to try to understand the mutations at the root of the disease.
Without fail, each patient's leukemia cells held hundreds of mutations, posing a conundrum for scientists, who have long believed that all the mutations in a cancer cell are likely to be important for the disease to progress.
"But we knew all of these mutations couldn't be important," says co-
|Contact: Caroline Arbanas|
Washington University School of Medicine