According to a study due to be published in the March 22 issue of the New England Journal of Medicine, a set of genetic abnormalities in individuals with acute myelogenous leukemia (AML) have been identified by researchers at Memorial Sloan-Kettering Cancer Center. This set of genetic abnormalities can help doctors to more accurately predict patients' prognoses as well as select therapies that are most likely beneficial for the patient.

Ross Levine, M.D., lead author of the study, member of Memorial Sloan-Kettering's Human Oncology Pathogenesis Program, and a medical oncologist on the Leukemia Service at Memorial Sloan-Kettering, said:

"Our study shows that genetic profiling makes it possible to more precisely categorize which patients are most likely to have their leukemia return after treatment.

We also want to use existing therapies more intelligently. It helps a great deal to know which subset of patients will actually benefit from intensive therapies, such as a higher dose of chemotherapy or a bone marrow transplant."

Currently, there are just a few known genetic biomarkers that clinicians rely on in order to predict outcome in individuals suffering with leukemia. Although these biomarkers provide helpful information for some patients with AML, for the majority it is hard to predict the chance for a cure.

The researchers used a method that incorporated information from a set of genes. This allowed them to categorize almost two-thirds of patients into clearly defined prognostic groups.

Dr. Levine, explained:

"Our goal was not to ask whether a certain gene or two raised or lowered risk, but to determine whether a combination of characteristics from a set of genes made it possible to precisely stratify patients according to risk."
The team examined blood or bone marrow samples from 502 individuals with AML who took part in a clinical trial conducted by Martin S. Tallman, M.D., Chief of Memorial Sloan-Kettering's Leukemia Service. The aim of the trial was to determine whether increasing the standard dose of chemotherapy would improve survival for individuals with AML under the age of 60.

The genetic analysis was performed by a team of researchers from Memorial Sloan-Kettering, Weill Cornell Medical College, and other institutions. During the analysis they examined the samples for mutations, or abnormalities, within 18 genes known to have variations in individuals with acute myelogenous leukemia.

The scientists examined the relationship between the mutations present in each participant and how well they coped with disease after receiving either the standard or increased chemotherapy dose.

Dr. Tallman, who is co-author of the new study, explained:

"Our findings have important clinical implications for patients with AML, demonstrating that genetic profiling can improve current prognostic models and help guide therapeutic decisions so patients have an optimal result.

Moving forward, the challenge will be to provide this genetic information in a timely and affordable way to influence treatment decisions prospectively."

With this analysis they were able to determine specific risk levels for a range of gene-mutation combinations. In addition, the researchers found that only some patients in the trial benefited from higher chemotherapy dose.

They took into consideration factors, such as gender and age, and validated the results in a separate group of patients in order to make sure that the profiling method will be generally applicable beyond the current study.

Dr. Levine and his colleagues are currently in the process of translating the study results into clinical use.

Dr. Levine, explained:

"We've already developed genetic tests, which can be used to test for this set of mutations in patients, and we're in the process of making sure they work well in practice. We have preliminary evidence that they perform well, and we're hoping to have a pilot study soon as a step toward getting it into the clinic. We want to show this approach can be used not just at Memorial Sloan-Kettering but throughout the leukemia community."

According to an estimate by The American Cancer Society, in 2012, 13,780 individuals in the U.S. will be diagnosed with AML, and over 10,000 will die from the disease.

Written by Grace Rattue