Metzeler KH et al. (2008) An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia. Blood 112: 4193–4201

In patients with acute myeloid leukemia (AML), chromosomal abnormalities can affect gene-expression profiles and, therefore, genes that have been identified as having a predictive role might not represent suitable prognostic factors for outcome in patients with cytogenetically normal AML (CN-AML). Metzeler et al. recently reported a 66-gene signature that predicts overall survival in patients with CN-AML.

The authors analyzed data from 163 adult patients with CN-AML who were enrolled in the AMLCG 1999 trial and had received intensive induction and consolidation chemotherapy. Gene-expression profiling was performed using microarrays. A supervised principal components analysis identified 86 probe sets that corresponded to 66 genes significantly associated with overall survival. When the authors analyzed the treatment outcomes in an independent group of 79 CN-AML patients, a high-risk genotype score was a significant negative prognostic factor for overall survival and event-free survival (P = 0.002 and P = 0.001, respectively). Moreover, in patients in complete remission, a high-risk genotype score was associated with reduced relapse-free survival (P = 0.025). In a validation cohort of 64 patients treated in the CALGB 9621 study, this risk score was also negatively associated with overall survival and event-free survival (P <0.001). Patients with a high-risk score in complete remission had reduced relapse-free survival (P <0.001). After adjusting for age, the ratio between FLT3 alleles with internal tandem duplications: wild type and NPM1 mutation status, and the gene-expression score continued to predict overall and event-free survival.

This novel gene signature predicts outcome in patients with CN-AML. Future studies assessing its clinical utility in AML patients with aberrant karyotypes are warranted.