Radmacher MD et al. (2006) Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B study. Blood 108: 1677–1683

Patients with acute myeloid leukemia (AML) and a normal karyotype comprise the largest cytogenetic group of AML. A recent study by Bullinger et al. identified a signature based on differential gene expression that characterized two separate subgroups of patients with cytogenetically normal AML according to their predicted outcome. Radmacher et al. sought to independently validate the prognostic significance of this signature in a larger group of patients.

Pretreatment samples from 64 uniformly treated adults with cytogenetically normal AML were characterized for prognostic biomarkers, including FLT3 internal tandem duplication, and clustered into poor or good outcome groups according to the Bullinger signature; gene expression was measured using oligonucleotide microarrays. The association of the signature with patient outcome was determined using cluster analysis.

The authors confirmed significant differences in both overall survival and disease-free survival between the cluster-defined patient subgroups (P = 0.02 and P = 0.05, respectively). Furthermore, they developed a prognostic classification system derived from the gene-expression signature that could predict outcome for individual patients. A strong association was observed between the outcome classifier and FLT3 internal tandem duplication.

Progress is being made in gene-expression profiling of AML patients with normal cytogenetics. The challenge for the future is to increase the prognostic utility of expression signatures and incorporate these biological developments into novel risk-adapted therapeutic strategies.