DNMT3A mutations linked to adverse outcomes in patients with acute myeloid leukemia
Wednesday, November 10, 2010 (Last Updated: 11/11/2010)
WEDNESDAY, Nov. 10 (HealthDay News) -- Researchers have identified genetic mutations that appear to be associated with adverse outcomes in people with acute myeloid leukemia (AML). Their research has been published online Nov. 10 in the New England Journal of Medicine.
Timothy J. Ley, M.D., of Washington University in St. Louis, and colleagues identified a somatic mutation in DNMT3A, encoding a DNA methyltransferase, in the genome of cells from an AML patient with a normal karyotype. They sequenced the exons of DNMT3A in 280 more AML patients.
The researchers found that DNMT3A mutations were predicted to affect translation in 62 (22.1 percent) of the patients. They also found 18 different missense mutations, the most ubiquitous of which was predicted to affect an amino acid, in 37 patients. DNMT3A mutations were associated with poor outcomes in patients with FLT3 mutations or an intermediate-risk cytogenetic profile. Median overall survival among patients with the mutations was significantly shorter than among those without them (12.3 versus 41.1 months).
"DNMT3A mutations are highly recurrent in patients with de novo AML with an intermediate risk cytogenetic profile and are independently associated with a poor outcome," the authors write.
A co-author disclosed financial ties to Novartis, Athersys, and Celgene.
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