Identification of genes differentially regulated by the P210BCR/ABL1 fusion oncogene using cDNA microarrays
Identification of genes differentially regulated by the P210BCR/ABL1 fusion oncogene using cDNA microarrays
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DOI：
10.1016/j.exphem.2004.02.012
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发表时间：
2004-05-01
影响因子：
2.6
通讯作者：
Meltzer, PS
中科院分区：
文献类型：
--
作者：
Håkansson, P;Segal, D;Meltzer, PS
Objective. t（9;22）易位与超过95%的慢性髓细胞白血病病例相关。BCR和ABL 1位点的融合产生组成型活性BCR/ABL 1酪氨酸激酶。BCR/ABL 1可激活多种信号转导分子，包括MYC、PI-3激酶和不同的STAT分子。相反，已知相对较少的基因在转录水平上受BCR/ABL 1调节。为了更好地理解BCR/ABL 1激活的转录程序，我们使用cDNA微阵列评估了通过四环素诱导型启动子表达P210 BCR/ABL 1的U937骨髓单核细胞中约6450个人类基因的相对表达。我们证实了先前报道的BCR/ABL 1上调PIM 1和JUN癌基因。此外，我们还鉴定了59个被BCR/ABLI上调的基因。有趣的是，这些基因中大约有三分之一是以前报道的干扰素（IFN）应答基因，包括OAS 1，IFIT 1，IFI 16，ISGF 3G和STAT 1基因。另外7个BCR/ABL 1调节基因在U937细胞中被发现是IFN应答的。表达谱还包括编码转录因子、激酶和信号转导分子的基因，以及调节细胞生长、分化、凋亡和细胞粘附的基因，这些特征以前被认为受到BCR/ABLI的影响。这些观察为BCR/ABL 1作用机制提供了新的见解，并为进一步研究提供了一系列靶点。(C)2004年国际实验血液学学会。爱思唯尔公司出版
Objective. The t(9;22) translocation is associated with more than 95% of cases of chronic myeloid leukemia. The resulting fusion of the BCR and ABL1 loci produces the constitutively active BCR/ABL1 tyrosine kinase. A wide range of signal transduction molecules are activated by BCR/ABL1, including MYC, PI-3 kinase, and different STAT molecules. In contrast, relatively few genes are known to be regulated by BCR/ABL1 at the level of transcription.Materials and Methods. In an effort to better understand the transcriptional program activated by BCR/ABL1, we used cDNA microarrays to evaluate the relative expression of approximately 6450 human genes in U937 myelomonocytic cells expressing P210 BCR/ABL1 via a tetracycline-inducible promoter.Results. We confirmed the previously reported up-regulation of the PIM1 and JUN oncogenes by BCR/ABL1. In addition, we identified 59 more genes up-regulated by BCR/ABLI. Interestingly, roughly one third of these were genes previously reported to be interferon (IFN)-responsive, including the OAS1, IFIT1, IFI16, ISGF3G, and STAT1 genes. An additional seven BCR/ABL1-regulated genes were found to be IFN-responsive in U937 cells. The expression profile also included genes encoding transcription factors, kinases, and signal transduction molecules, as well as genes regulating cell growth, differentiation, apoptosis, and cell adhesion, features previously suggested to be affected by BCR/ABLI.Conclusion. These observations shed novel insight into the mechanism of BCR/ABL1 action and provide a range of targets for further investigation. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.