Menacing Marker

Mutation Signals High Recurrence Risk in Older AML Patients

Clara BloomfieldOlder patients with acute myeloid leukemia (AML) and normal-looking chromosomes in their cancer cells have a higher risk of recurrence if they have mutations in the ASXL1 gene, according to a study by OSUCCC – James researchers.

The study is the first to investigate the influence of these mutations on prognosis in patients with cytogenetically normal AML (CNAML) and in conjunction with other prognostic gene mutations. It also reports the first gene-expression signature for CN-AML with mutated ASXL1.

“Our findings could lead to more effective targeted therapies and improved cure rates for these patients,” says principal investigator Clara D. Bloomfield, MD, a Distinguished University Professor who also serves as cancer scholar and senior adviser to the OSUCCC – James.

Bloomfield and colleagues found that patients age 60 and older with CN-AML and ASXL1 mutations had significantly shorter survival than patients with the normal gene – only 5 percent of patients with the mutation were alive after three years, compared with 23 percent of patients without the mutation. Complete remission rates were also significantly lower, at 53 percent for patients with versus 71 percent for
patients without the mutation. The findings were presented at the 53rd Annual Meeting of the American Society of Hematology. The study’s first author, Klaus Metzeler, MD, a research fellow at the OSUCCC – James, received an “Abstract Achievement Award” for this novel and clinically relevant work.

“Mutations in the ASXL1 gene appear to be an important marker of poor prognosis in older AML patients,” says Bloomfield, Metzeler’s mentor. “Importantly, their negative impact was greatest in patients who, based on established genetic markers, would be expected to have favorable outcomes.

ASXL1 mutations therefore identify a previously unknown high-risk subgroup in older AML patients,” she adds. “These patients don’t do well with current standard therapy and may be candidates for treatment with novel drugs in a clinical trial.”

Published in the journal Blood.

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