Genetic predictors of AML outcome get more specific

Advanced profiling of gene mutations in acute myeloid leukemia (AML) could potentially be used to help predict prognosis and guide treatment decisions, according to recent study findings.

Ross L. Levine, MD, of Memorial Sloan-Kettering Cancer Center in New York, New York, and colleagues analyzed 18 genes in 398 persons younger than 60 years with AML who had participated in the phase 3 Eastern Cooperative Oncology Group (ECOG) E1900 clinical trial. In that study, patients had been randomly assigned to receive induction therapy with high-dose or standard-dose daunorubicin. Levine's team also used an independent cohort of 104 patients from the same trial to validate the findings of the analysis.

Although previous studies have suggested that analysis of CEBPA, NPM1, and FLT3-ITD mutations can be used to stratify risk among patients with intermediate-risk AML, Levine's group found that more extensive mutational analysis can better discriminate patients with AML into various prognostic groups of “favorable,” “intermediate,” and “unfavorable.” For example, patients without FLT3-ITD mutations and with both mutant NPM1 and IDH represent a favorable-risk subset defined by a specific mutational genotype. By comparison, patients who were negative for FLT3-ITD mutations and had mutant NPM1 but no IDH mutations had a much less favorable outcome, particularly if they had concurrent mutations associated with an unfavorable-risk profile.

As the investigators explained in The New England Journal of Medicine (www.nejm.org/doi/pdf/10.1056/NEJMoa1112304), their data show that mutational analysis of a larger set of genetic alterations than currently used in the clinical setting could be applied to classify patients with AML into more precise risk-based subgroups. This approach could be used to identify patients most likely to benefit from standard AML therapy, allogeneic stem-cell transplantation, participation in a clinical trial, or other treatments. 

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