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

应用Affymetrix基因芯片HGU95Av2芯片分析AML伴形态异常的基因表达谱，旨在建立一种新的AML分类系统。从11例AML伴三系异型增生、15例初发AML无异型增生和11例MDS后AML中分离CD133阳性白血病细胞，检测约12000个基因的表达。根据这些基因的表达谱，(1)和(3)类AML病例用主成分明确地分开。分析。虽然(1)和(3)类病例存在形态异常，但它们具有不同的生物学背景。在基因表达分析中，髓过氧化物酶(MPO)基因似乎存在差异表达。实时荧光定量聚合酶链式反应显示，与(2)组相比，(1)组的MPO基因表达水平较低。MPO基因的高表达与预后良好相关，提示根据基因表达对AML进行分类是有用的和有意义的。另一个候选基因，层粘连蛋白受体，似乎也与AML细胞的核型有关。这些观察表明，这些基因的表达将有助于某些AML病例的分类，它们对于了解AML生物学的洞察力也很重要。

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.