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Recurrent Mutations Seen in Acute Myeloid Leukemia

Last Updated: August 05, 2009.


Whole-genome sequencing suggests 12 mutations play a key role in AML pathogenesis

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In acute myeloid leukemia, recurring mutations may play an important role in pathogenesis, according to a study published online Aug. 5 in the New England Journal of Medicine.

WEDNESDAY, Aug. 5 (HealthDay News) -- In acute myeloid leukemia (AML), recurring mutations may play an important role in pathogenesis, according to a study published online Aug. 5 in the New England Journal of Medicine.

Elaine R. Mardis, Ph.D., of Washington University in St. Louis, and colleagues performed whole-genome sequencing on samples of bone marrow and skin from a 38-year-old male patient with AML-M1.

The researchers found that the AML genome contains about 750 somatic point mutations, but that only 12 of them are likely to play an important role in pathogenesis. They found mutations in two genes (NRAS and NPM1) which had previously been identified in patients with AML. They also found two previously unidentified mutations, including one in the IDH1 gene that recurred in 15 of 187 additional AML genomes, and one in a genomic region with regulatory potential that recurred in one additional tumor.

"We now know IDH1 mutations occur in both AML and glioblastoma multiforme, two very different types of cancer. How these mutations contribute to such tumors and whether the various IDH1 mutations have differential effects on neural cells and myeloid cells are questions that must be answered," states the author of an accompanying editorial.

Authors of the study reported financial relationships with pharmaceutical and medical companies.

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