Gene’s Activity Points to More Lethal Subtype of AML

A new study shows that the activity of a particular gene can identify people who have a more lethal form of acute myeloid leukaemia, singling out those patients who should receive more intense therapy.

The gene, called ERG (for ETS-related gene), has also been linked to chronic leukaemia and to breast and prostate cancer. The findings apply to acute myeloid leukaemia (AML) patients with leukaemia cells that have normal-looking chromosomes, a feature that occurs in about half of AML patients. Among these patients, those with leukaemia cells showing high ERG activity are almost six times more likely to relapse or die within five years than are patients with low ERG expression following standard therapy. The Cancer and Leukaemia Group B study was initiated by researchers at the Ohio State University Comprehensive Cancer Center, and their findings were published online in the Journal of Clinical Oncology. “Our study shows that high ERG activity predicts a poor prognosis in these patients, even when other molecular markers are taken into consideration,” says first author Guido Marcucci, associate professor of internal medicine and an AML specialist at Ohio State’s James Cancer Hospital and Solove Research Institute. “The findings mean that these patients require a stem-cell transplant or other aggressive therapy, and that patients with low ERG activity can be treated using standard therapy.” The research confirms a 2005 study led by the same Ohio State researchers in a completely independent set of patients, Marcucci says. “Both studies together further refine the molecular classification of AML in this group of patients and should help us improve treatment outcomes,” says principal investigator Clara D. Bloomfield, professor of internal medicine, and an internationally recognized specialist in AML. About 13,400 new cases of AML are expected this year, and a little more than half will have leukaemia cells with normal-looking chromosomes. The rest will have chromosomes that show distinctive damage. In these patients, the type of damage helps doctors determine the best therapy and an individual’s prognosis. In 2005, Bloomfield, Marcucci and colleagues were the first to show that high ERG levels predicted a poor response to therapy in patients whose cancer cells have normal-looking chromosomes. The present study was designed to verify that finding in a separate group of 76 AML patients under 60 years of age. It also took into consideration other genetic markers that signal whether the disease will respond well or poorly to standard therapy. “We showed very similar results in this completely separate group of patients,” Marcucci says. “After two years, only 29 percent of patients with high ERG were disease-free and alive versus 53 percent of patients with low ERG activity.” Funding from the National Cancer Institute and The Coleman Leukaemia Research Foundation supported this research. (Source: Journal of Clinical Oncology : Ohio State University : August 2007)