Savli H, Sunnetci D, Cine N, Gluzman D F, Zavelevich M P, Sklyarenko L M, Nadgornaya V A, Koval S V
Medical Genetics Department, Medicine Faculty of Kocaeli University, Turkey.
Exp Oncol. 2012;34(1):57-63.
Genetic mechanisms that result in the development and progression of B-cell chronic lymphocytic leukemia (B-CLL) are mainly unknown. We have analyzed gene expression patterns in Ukrainian B-CLL patients with the aim of identifying B-CLL involved / associated genes in order to shed light on the biology of this pathological entity.
The samples of the peripheral blood and bone marrow of 44 Ukrainian B-CLL patients with no characteristics indicative of unfavorable course of the disease such as CD38 were analyzed morphologically and immunocytochemically according to the new WHO classification. Total RNA was isolated, and gene expression levels were determined by microarray method comparing with the sample from 17 healthy donors.
We investigated interactions using the Ingenuity Pathway Analysis (IPA) software and found 1191 network eligible up-regulated genes and 3398 Functions/Pathways eligible up-regulated genes, 1225 network eligible down-regulated genes and 2657 Functions/Pathways eligible down-regulated genes.
In B-CLL patients, gene networks around MYC, HNF1A and HNF4A, YWHAG, NF-κB1 and SP1 are identified as up-regulated; CEBPA, YWHAG, SATB1 and RB1 -- as down-regulated. G protein coupled receptor signaling, arachidonic acid and linoleic acid metabolisms, calcium signaling, metabolism of xenobiotics by cytochrome P450 are found out as significant up-regulated pathways. EIF2 and Cdc42 signaling, regulation of eIF4 and p70S6k signaling, protein ubiquitination pathway and oxidative phosphorylation are the most significant down-regulated pathways obtained in our study. The involvement of NF-κB gene network and upregulated levels of G protein coupled receptor signaling pathway, which has an important role in transcription of NF-κB, are important and need further examination.
导致B细胞慢性淋巴细胞白血病（B-CLL）发生和进展的遗传机制主要尚不清楚。我们分析了乌克兰B-CLL患者的基因表达模式，旨在识别与B-CLL相关的基因，以便阐明这一病理实体的生物学特性。
对44例无CD38等提示疾病不良病程特征的乌克兰B-CLL患者的外周血和骨髓样本，按照世界卫生组织新分类标准进行形态学和免疫细胞化学分析。提取总RNA，通过微阵列法与17名健康供体的样本比较来测定基因表达水平。
我们使用Ingenuity Pathway Analysis（IPA）软件研究相互作用，发现1191个符合网络上调标准的基因和3398个符合功能/通路上调标准的基因，1225个符合网络下调标准的基因和2657个符合功能/通路下调标准的基因。
在B-CLL患者中，MYC、HNF1A和HNF4A、YWHAG、NF-κB1和SP1周围的基因网络被确定为上调；CEBPA、YWHAG、SATB1和RB1为下调。G蛋白偶联受体信号传导、花生四烯酸和亚油酸代谢、钙信号传导、细胞色素P450对外源生物的代谢被发现是显著上调的通路。EIF2和Cdc42信号传导、eIF4和p70S6k信号传导的调节、蛋白质泛素化途径和氧化磷酸化是我们研究中最显著下调的通路。NF-κB基因网络的参与以及在NF-κB转录中起重要作用的G蛋白偶联受体信号通路的上调水平很重要，需要进一步研究。
