It's Normal Aging - Not Cancer

Acute Myeloid Leukemia requires only a few genetic changes to form

(RxWiki News) Our cells are constantly changing, just like we are. These include mutations that occur over a lifetime, all of which are part of normal aging. Add in a few more mutations, though, and you've got cancer.

Acute myeloid leukemia (AML) develops not after hundreds of cell mutations, but only a few, researchers have recently learned.

"Never ignore fatigue."

Scientists at Washington University School of Medicine in St. Louis made the discovery.

"Now we have a very accurate picture of how acute leukemia develops," said 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."

AML happens when too many immature blood cells overwhelm healthy blood cells. Washington University scientists have sequenced the entire genome of 200 patients to learn how the disease evolves.

Researchers were surprised to learn that the patient's leukemia cells had hundreds of mutations. It's been believed that all mutations in a cancer cell play a role in the disease.

"But we knew all of these mutations couldn't be important," said co-first author Daniel Link, MD, professor of medicine. "It didn't make any sense to us that so many mutations were present in all the cells in the tumor."

To learn how these mutations occurred, the team gathered and analyzed blood stem cells - the immature cells in the bone marrow that produce all blood cells - from people ranging in age from a few days to 70 years.

Everybody has roughly 10,000 blood stem cells in their bone marrow. Each of the cells has about 10 mutations a year. So by the time a person is 60, they will have naturally acquired 600 mutations in every single blood stem cell.

After sequencing AML cells and comparing them to healthy cells, scientists were surprised that folks with leukemia had about the same number of mutations as healthy individuals.

"AML is relatively uncommon until about age 60," said 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."

The study also uncovered 13 so-called "driver" mutations that play a role in the leukemia developing. Along with the presence of these drivers, scientists found that only one or two more mutations were needed to get AML started.

This research was published July 20 in the journal Cell.

It was supported by the National Human Genome Research Institute, the National Cancer Institute and the Barnes-Jewish Hospital Foundation.

Financial disclosures weren't publicly available.

Review Date: 
July 25, 2012