Expanded Tumor Profiling Yields Clues about Acute Myeloid Leukemia ► NCI Cancer Bulletin for March 20, 2012 - National Cancer Institute

NCI Cancer Bulletin for March 20, 2012 - National Cancer Institute

Expanded Tumor Profiling Yields Clues about Acute Myeloid Leukemia

Testing the cancer cells of patients with acute myeloid leukemia (AML) for alterations in a panel of 18 genes could help doctors predict the risk of relapse for individual patients, according to a retrospective analysis of data from a large clinical trial. This approach—sometimes called cancer profiling—could also provide information about which patients may benefit most from certain treatments. The findings appeared in the March 14 New England Journal of Medicine.
Doctors use various methods to diagnose AML and to classify patients according to the risk of relapse. Some patients have their cancers profiled for alterations in three genes associated with AML. The new study suggests, however, that analyzing a larger set of genes could help doctors assign patients to more precise subgroups, with favorable, intermediate, or unfavorable risk profiles.
To reach this conclusion, Dr. Ross Levine of Memorial Sloan-Kettering Cancer Center and his colleagues profiled stored samples from nearly 400 participants in a large clinical trial led by the Eastern Cooperative Oncology Group (ECOG) and published in 2009. The researchers then validated their findings using an independent group of 104 patients from the same trial.
At least one cancer-related genetic alteration was found in 97 percent of the patients. Certain mutations tended to occur together, revealing clues to the pathways that are active in AML, the researchers noted. In addition, the expanded panel yielded better prognostic information than the one currently used in the clinic.
“Some of the newly discovered mutations substantially improved the classification of patients as having either a favorable or unfavorable risk profile,” Dr. Levine said.
He noted that profiling cancers may also inform decisions about treatment. Results from the ECOG trial showed that AML patients under 50 years of age may benefit from a higher dose of daunorubicin chemotherapy early in treatment. The new analysis, however, found that some patients benefited more than others.
Specifically, higher-dose daunorubicin chemotherapy improved survival among patients whose cancer cells had DNMT3A or NPM1 gene mutations or MLL gene translocations but not among patients with cancer cells that lacked these gene alterations. These findings need to be confirmed, the authors noted.
Future studies will seek to identify additional genetic and epigenetic events that contribute to AML. “The challenge will be to not look at each alteration as an independent variable, but instead to see whether new alterations—together with other known mutations—improve prognostic models and inform the selection of treatments,” Dr. Levine said.
The new study shows what can be learned by analyzing DNA samples and data from a completed clinical trial, noted Dr. Lucy Godley of the University of Chicago Medical Center, who wrote an accompanying editorial. “Dr. Levine essentially took samples from the freezer and used them to ask new questions about AML.”