Differential expression of drug resistance-related genes between sensitive and resistant blasts in acute myeloid leukemia
Differential expression of drug resistance-related genes between sensitive and resistant blasts in acute myeloid leukemia
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DOI：
10.1159/000096854
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发表时间：
2007-01-01
影响因子：
2.4
通讯作者：
Flasshove, M.
中科院分区：
文献类型：
--
作者：
Eisele, L.;Klein-Hitpass, L.;Flasshove, M.
耐药性是急性髓细胞白血病（AML）治疗中的一个重要问题。为了确定可能与耐药相关的基因，我们回顾性研究了14例初治AML患者的原始细胞群体中的基因表达模式，重点研究了已知或潜在的阿糖胞苷和蒽环类药物耐药机制。诱导化疗和缓解后化疗后，7例患者达到完全缓解（CR）超过1年，而7例患者在诱导化疗和挽救化疗后显示原始细胞持续（BP）。使用从存档的胍提取物中提取的RNA和Affymetrix HGU 133 A基因芯片进行基因表达分析。我们利用基因本体分类生物过程来选择与DNA代谢、核苷和核苷酸代谢和转运、活性氧代谢、细胞凋亡和药物反应有关的基因，并鉴定了32个差异表达基因。从这个功能的角度来看，我们发现CR组和BP组在核苷酸代谢（PBEF 1，G6 PD; p = 0.048），细胞凋亡（TNFAIP 3，TNFAIP 8，MPO，BCL 2A 1，BAX，SON，BNIP 3L; p = 0.039）和活性氧代谢（SOD 2，KIAA 0179; p = 0.048）方面存在差异。然而，试图建立一个预测模型的化疗耐药性失败。BP样品的CD 34表达比CR样品高2倍。因此，我们的研究结果与描述CD 34+和CD 34-原始细胞群体之间凋亡抗性差异的报告一致。两者合计，我们的研究结果表明，耐药性AML是一种异质性的现象，可能更好地定义通过干扰的生物过程，而不是通过专注于不同基因的表达的改变。版权所有（c）2007 S. Karger AG，巴塞尔。
Drug resistance constitutes a considerable problem in the therapy of acute myeloid leukemia (AML). In order to identify genes which might be related to drug resistance, we retrospectively studied gene expression patterns in blast populations of 14 patients with de novo AML, focusing on known or potential resistance mechanisms against cytosine arabinoside and anthracyclines. Following induction and postremission chemotherapy, 7 patients achieved a complete remission (CR) for more than 1 year, while 7 patients showed blast persistence ( BP) after induction and salvage chemotherapy. Gene expression analysis was performed using RNA extracted from archived guanidine extracts and Affymetrix HGU133A gene chips. We utilized the Gene Ontology category Biological Process to select genes implicated in DNA metabolism, nucleoside and nucleotide metabolism and transport, reactive oxygen species metabolism, apoptosis and response to drugs and identified 32 differentially expressed genes. From this functional perspective, we found differences between the CR and BP groups with regard to nucleotide metabolism (PBEF1, G6PD; p = 0.048), apoptosis (TNFAIP3, TNFAIP8, MPO, BCL2A1, BAX, SON, BNIP3L; p = 0.039) and reactive oxygen species metabolism (SOD2, KIAA0179; p = 0.048). However, the attempt to construct a predictive model of chemoresistance failed. BP samples had a 2-fold higher expression of CD34 than CR samples. Thus, our findings are in line with reports describing differences in apoptosis resistance between CD34+ and CD34- blast populations. Taken together, our results suggest that drug resistance in AML is a heterogenous phenomenon that might be better defined by means of disturbed biological processes than by focusing on the alteration of the expression of distinct genes. Copyright (c) 2007 S. Karger AG, Basel.