本实验还探讨了mdr1基因与AML病人临床耐药及疗效的关系,结果显示,AML病人临床耐药与mdr1基因阳性表达密切相关,临床耐药组mdr1阳性表达率显著高于非耐药组;mdr1基因阴性表达组的CR率明显高于mdr1基因阳性表达组,mdr1基因阳性表达严重影响CR率。因此我们推测,mdr1基因阳性表达是判断病人对诱导治疗是否耐药的可靠预测指标,可作为检测临床耐药和判断预后的指标之一。有研究结果还表明,部分mdr1基因表达阴性的病人也出现了耐药,提示耐药现象的出现不是单一的一种基因或蛋白参与的结果[8]。谭耀红等[9]在分析K562/A02细胞的耐药机制时发现,mdr1 mRNA明显升高,TOPⅡmRNA明显下降,Bcl?2表达增高,GST活性增强,端粒酶活性增强,P?gp和sorcin过表达,进一步说明了耐药机制的复杂性。
【参考文献】
[1]YANG C Z, LUAN F J, XIONG D S, et al. Multidrug resistance in leukemic cell Lane K562/A02 induced by doxorubicin[J]. Acta Pharmacologica Sinica, 1995,16(4):333?337.
[2]BAILLY J D, MULLER C, JAFFREZOU J P, et al. Lack of correlation expression and function of P?glycoprotein in acute leukemia[J]. Leukemia, 1995,9:799?807.
[3]LEE W P. Purification, cDNA cloning and expression of human sorcin in vincristine? resistance HOB1 lymphoma cell lines[J]. Arch Biochem Biophysic, 1996,325(2):217?226.
[4]LOO T W, BARTLETT M C, CLARK D M. Substrate?induced conformational changes in the transmembrane segments of human P?glycoprotein. Direct evidence for the substrate?induced fit mechanism for drug binding[J]. J Biol Chem, 2003,278:13603 ?13606.
[5]吴少玲,张殿红,贾秀珍. nm232H1基因在急性白血病中表达及与多药耐药关系[J]. 齐鲁医学杂志, 2005,20(2):122?125.
[6]孟繁军,罗兵,曲彦. 急性白血病多药耐药基因MDR1表达及临床意义[J]. 青岛医学院学报, 1999,35(3):181?183.
[7]WANG Y H, MOTOJI T, MOTOMURA S, et al. Recovery of drug sensitivity by MS209, a new multidrug resistance reversing agent, on acute myelogenous leukemia blasts and K562 cells resistant to adriamycin cell line[J]. Eur J Haematol, 1997,58:186?194.
[8]TAN Y H, LI G Y, ZHAO C H, et al. Expression of sorcin predicts poor outcome in acute myeloid leukemia[J]. Leukemia Research, 2003,27(2):125?131.
[9]谭耀红,赵春华,杨纯正. 用cDNA Array分析K562/A02细胞多药耐药机制[J]. 中国医学科学院学报, 2001,23(3):272?274.