Nowicki Michal Oskar, Pawlowski Peter, Fischer Thomas, Hess Georg, Pawlowski Tomasz, Skorski Tomasz
Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.
Oncogene. 2003 Jun 19;22(25):3952-63. doi: 10.1038/sj.onc.1206620.
To obtain comprehensive information about the genes involved in BCR/ABL-dependent leukemogenesis, samples from 15 chronic myelogenous leukemia (CML) patients and seven normal donors were analysed using a cDNA microarray assay. After subtraction of the artificial, random or cross-hybridization signals, data about 5315 genes have been effectively analysed in all samples. The assay revealed >/=4-fold difference in the average expression of 263 genes in all CML samples when compared to normal counterparts, with 148 genes being upregulated and 115 being downregulated. Differentially expressed genes include those associated with BCR/ABL-induced abnormalities in signal transduction, gene transactivation, cell cycle, apoptosis, adhesion, DNA repair, differentiation, metabolism and malignant progression. Interestingly, CML-blast crisis cells in peripheral blood differ from those from bone marrow, indicating major changes in gene expression profiles upon entering into the bloodstream. Moreover, BCR/ABL modulates expression of genes, which are involved in regulation of chromosome/chromatin/DNA dynamics during S and M cell cycle phase. Moreover, the ability of CML cells to recognize and respond to a pathogen infection may be compromised. Altogether, this work provides a large body of information regarding gene expression profiles associated with CML and also represents a source of potential targets for CML therapeutics.
为了获取有关BCR/ABL依赖性白血病发生所涉及基因的全面信息,使用cDNA微阵列分析方法对15例慢性粒细胞白血病(CML)患者和7名正常供体的样本进行了分析。在扣除人工、随机或交叉杂交信号后,对所有样本中约5315个基因的数据进行了有效分析。该分析显示,与正常样本相比,所有CML样本中263个基因的平均表达差异≥4倍,其中148个基因上调,115个基因下调。差异表达的基因包括那些与BCR/ABL诱导的信号转导、基因反式激活、细胞周期、凋亡、黏附、DNA修复、分化、代谢和恶性进展异常相关的基因。有趣的是,外周血中的CML原始细胞危象与骨髓中的不同,这表明进入血液后基因表达谱发生了重大变化。此外,BCR/ABL调节在S期和M期细胞周期中参与染色体/染色质/DNA动态调节的基因的表达。此外,CML细胞识别和应对病原体感染的能力可能会受到损害。总之,这项工作提供了大量有关与CML相关的基因表达谱的信息,也代表了CML治疗潜在靶点的来源。