AML score that combines genetic and epigenetic changes might help guide therapy

PUBLIC RELEASE DATE:

8-Jan-2014

Contact: Darrell E. Ward Darrell.Ward@osumc.edu 614-293-3737 Ohio State University Wexner Medical Center

COLUMBUS, Ohio Currently, doctors use chromosome markers and gene mutations to determine the best treatment for patients with acute myeloid leukemia (AML). But a new study suggests that a score based on seven mutated genes and the epigenetic changes that the researchers discovered were also present might help guide treatment by identifying novel subsets of patients.

The findings, published in the Journal of Clinical Oncology, come from a study led by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James).

The epigenetic change used in the study is DNA methylation. It involves the addition of methyl groups to DNA, which can reduce or silence a gene's activity, or expression. Abnormal DNA methylation alters normal gene expression and often plays an important role in cancer development.

Overall, the findings suggest that patients with a low score indicating that one or none of the seven genes is overexpressed in AML cells had the best outcomes, and that patients with high scores that is, with six or seven genes highly expressed had the poorest outcomes.

"To date, disease classification and prognostication for AML patients have been based largely on chromosomal and genetic markers," says principal investigator Clara D. Bloomfield, MD, Distinguished University Professor, Ohio State University Cancer Scholar and Senior Adviser.

"Epigenetic changes that affect gene expression have not been considered. Here we show that epigenetic changes in previously recognized and prognostically important mutated genes can identify novel patient subgroups, which might better help guide therapy," says Bloomfield, who is also the William Greenville Pace III Endowed Chair in Cancer Research at Ohio State.

The seven-gene panel was identified in 134 patients aged 60 and older with cytogenetically normal acute myeloid leukemia (CN-AML) who had been treated on Cancer and Leukemia Group B (CALGB)/Alliance clinical trials.

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AML score that combines genetic and epigenetic changes might help guide therapy