Gene Expression Profiles of CD133-positive Fractions Predict the Survival of Individuals with Acute Myeloid Leukemia

Abstract

Background: The current classification of acute myeloid leukemia (AML) is based predominantly on the cytogenetic abnormalities and morphology of the malignant blasts and is not always helpful for optimization of the treatment strategy. Gene expression profiles of AML blasts were obtained and a gene expression-based means of predicting the outcome of AML patients was developed. Materials and Methods: CD133-positive hematopoietic stem cell-like fractions were purified from the bone marrow of 99 individuals with AML-related disorders and the expression profiles of ~33,000 human transcripts in these cells were characterized with the use of DNA microarray analysis. Results: The comparison of the expression data between individuals with short- or long-term survival by application of Cox's proportional hazard model led to the identification of four genes, whose expression patterns discriminated between the two groups. The gene expression-based stratification (GES) system, based on a combination of the karyotype approach and the risk index calculated from the expression levels of the four outcome predictor genes, was developed to separate the patients into subgroups with distinct prognoses. Conclusion: DNA microarray analysis of purified fractions provides novel stratification schemes for AML based on the expression profiles of a handful of genes.