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Gene Mutations Seem to Make a Leukemia More Deadly
Date:11/10/2010

ntermediate-risk group, some of whom do poorly and some who don't, though scientists have been unable to figure out why.

"The purpose of this project was to sequence the genomes of many of the patients with intermediate risk to find mutations that are responsible for poor outcome so we can do a better job of treating them up front," Ley said.

The breakthrough in the project came after scientists decoded the genome of a woman who had died of AML and then compared that genome to the genome of her cancer cells.

For this paper, scientists report finding similar mutations in the DNMT3A (DNA methyltransferase 3A gene) gene in 22.1 percent of 280 other patients with AML.

The mutations were present in 34 percent of patients of intermediate risk but not all in patients with a favorable risk profile.

"It was a bonanza of mutations in this gene," Ley said, 34 in total.

And those with the mutations didn't do well, surviving for only about one year, compared to about three-and-a-half years in those without the mutation.

Those with the mutation also tended to fare better with bone marrow transplants, suggesting that this might be the first avenue of treatment for these patients.

Also, older patients did worse with the mutation. All 17 of patients over the age of 60 with the mutations had died by 18 months.

"We don't understand the mechanism yet," said Ley, who is hoping that other research groups will be able to validate the findings.

"This is another step toward getting a clearer picture of the biology involved in each patient's leukemia so we can better choose therapies for that specific patient and have the best chance to beat it," Rizzieri said.

More information

The Leukemia and Lymphoma Society has more on AML.

SOURCES: Timothy J. Ley, M.D., professor, medicine and genetics, Washington
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