Development of a new classification for AML based on the gene expression profile in leukemia stem cells.

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Gene expression profiles of AML with morphological dysplasia were analyzed using Affymetrix GeneChip HGU95Av2 microarrays aiming to develop a new classification system of AML. From (1) 11 cases of AML with trilineage dysplasia, (2) 15 cases of de novo AML without dysplasia and (3) 11 cases of AML following MDS, CD133 positive leukemia cells were separated and the expression of about 12000 genes was examined. Based on the expression profile of these genes, AML cases in category (1) and (3) were clearly separated with principal component. analysis. Although cases in category (1) and (3) have morphological dysplasia, they were shown to possess different biological backgrounds. During the analysis of gene expression, myeloperoxidase (MPO) gene seemed differentially expressed. Using real time quantitative PCR methods, the level of MPO gene expression was low among cases in category (1) compared to those in (2). The high level of MPO gene expression was associated wit better prognosis, suggesting that the classification of AML based on the gene expression was useful and meaningful. Another candidate gene, laminine receptor, also seemed t relate to the karyotype of AML cells. These observations suggested that the expression of those genes would be useful to classify certain cases of AML and they were important to see the insight of AML biology.