Scientists Map Genetic Evolution of Leukemia

Posted: March 15, 2012 at 6:25 am

Newswise The diagnosis of myelodysplastic syndrome, a blood cancer, often causes confusion. While some patients can be treated with repeated blood transfusions, others require chemotherapy, leaving some uncertainty about whether the syndromes actually are cancer.

Now, using the latest DNA sequencing technology, scientists at the Washington University School of Medicine in St. Louis have shown that the blood disease is an early form of cancer with characteristics that are very similar to the fatal leukemia to which it often progresses. And by mapping the genetic evolution of cancer cells in seven patients with myelodysplastic syndromes who later died of leukemia, they have found clues to suggest that targeted cancer drugs should be aimed at mutations that develop early in the disease.

The research, by a large team of Washington University researchers at the Siteman Cancer Center, appears online March 14 in the New England Journal of Medicine.

The scientists sequenced all the DNA the genome of tumor cells from the patients over time. While some cancer cells in each patient acquired new mutations as they evolved, they always retained the original cluster of mutations that made the cells cancerous in the first place.

This discovery, which must be confirmed in larger studies, suggests that drugs targeted to cancer mutations might be more effective if they are directed toward genetic changes in the original cluster of cancer cells called the founding clone. Drugs that target mutations found exclusively in later-evolving cancer cells may kill those cells but likely wouldnt damage founding clones that do not carry the later mutations.

Its probably not enough to know that a particular mutation exists in cancer cells, says senior author Timothy Graubert, MD, associate professor of medicine at the School of Medicine who also treats patients at Barnes-Jewish Hospital. We likely will need to dig deeper to find out whether a mutation is in the founding clone that initiated the cancer or in a later-evolving clone.

In other words, think of this cancer as a tree, Graubert says.

To kill a tree, you have to pull out the roots, he says. If you only cut off a limb, it will just grow back. Were saying that to be effective, targeted cancer drugs probably need to attack mutations at the root of this disease.

About 28,000 Americans are diagnosed with myelodysplastic syndromes each year, most over age 60. They occur when blood cells produced in the bone marrow dont fully develop and immature cells crowd out healthy ones. In about one-third of patients, the disease progresses to a fatal form of leukemia.

As part of the new research, Graubert and his colleagues teamed with researchers at Washington Universitys Genome Institute who sequenced the genomes of cancer cells after the patients developed acute myeloid leukemia. Then, they determined whether the mutations they found were present when the same patients were first diagnosed with myelodysplastic syndromes.

Excerpt from:
Scientists Map Genetic Evolution of Leukemia

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