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Adverse Effects of Mutations

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The genetic mutations that affect the survival chances of a patient with acute myeloid leukemia are, for the most part, unknown. But researchers at the University of Washington have found that mutations in DNMT3A are "independently associated with a poor outcome," as they report in the New England Journal of Medicine. Using massively parallel DNA sequencing, the team saw "a somatic mutation in DNMT3A, encoding a DNA methyltransferase, in the genome of cells from a patient with AML with a normal karyotype." And when they sequenced the exons of DNMT3A in 280 additional patients with de novo AML, the researchers saw that 22.1 percent of the patients had mutations in DNMT3A "that were predicted to affect translation." The mutations were highly enriched in a group of patients with a medium-risk cytogenetic profile, but completely absent in patients with a low-risk profile. "The median overall survival among patients with DNMT3A mutations was significantly shorter than that among patients without such mutations (12.3 months vs. 41.1 months)," the researchers write.

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