Leukemia Patients' Prognoses Predicted with Genetic Profiling

A set of genetic abnormalities have been identified in individuals with acute myelogenous leukemia (AML), a fast growing cancer of the blood and bone marrow.

These specific genetic abnormalities can help doctors to more accurately predict patients' prognoses as well as select therapies that are most likely beneficial for the patient.

Medical oncologists at the Memorial Sloan-Kettering Cancer Center (New York, NY, USA) examined blood or bone marrow samples from 502 individuals with AML who took part in a clinical trial. 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. DNA was analyzed from bone marrow in the case of 277/502 (55.2%) of the samples and from peripheral blood in the case of 225/502 (44.8%). Cytogenetic, fluorescent in situ hybridization and reverse-transcriptase polymerase chain reactions (RT-PCR) assays were performed for recurrent cytogenetic lesions in conjunction with the sequencing the coding regions of specific genes.

The scientists examined the samples for mutations, or abnormalities, within 18 genes known to have variations in individuals with acute myelogenous leukemia. They 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. With this analysis, they were able to determine specific risk levels for a range of gene-mutation combinations. In addition, the scientists found that only some patients in the trial benefited from higher chemotherapy dose.

Ross Levine, MD, the lead author of the study, said, "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." The study was published on March 14, 2012, in the New England Journal of Medicine (NEJM).

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Memorial Sloan-Kettering Cancer Center