Levels of expression of the mdr1 gene and glutathione S-transferase genes 2 and 3 and response to chemotherapy in multiple myeloma.
Levels of expression of the mdr1 gene and glutathione S-transferase genes 2 and 3 and response to chemotherapy in multiple myeloma.
复制标题
MDR1基因和谷胱甘肽S-转移酶基因2和3的表达水平以及多发性骨髓瘤对化学疗法的反应。
DOI：
10.1038/bjc.1992.95
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发表时间：
1992-03
影响因子：
8.8
通讯作者：
Woodcock, D M
中科院分区：
文献类型：
--
作者：
Linsenmeyer, M E;Jefferson, S;Wolf, M;Matthews, J P;Board, P G;Woodcock, D M
我们量化了mdr1基因（多药耐药表型）和谷胱甘肽s -转移酶基因GST-2和GST-3（也可以使多种细胞毒性药物失活）的多发性骨髓瘤患者骨髓样本中mrna的水平，并检查了这些基因表达水平与随后化疗反应之间的关系。47例患者中，37例接受化疗，34例可评价疗效。29名接受治疗的患者在骨髓取样之前没有接受过任何治疗，而8名患者之前接受过化疗。初始化疗无效患者的mdr1水平明显高于化疗有效患者（P = 0.01）。在骨髓瘤患者的总数据集中，mdr1和GST-2的mRNA水平显著相关（Spearman秩相关系数(r) = 0.54, P = 0.0004）， GST-2与GST-3的表达水平显著相关（r = 0.43, P = 0.017）。GST-3和mdr1水平与周相关性更强（r = 0.16, P = 0.4）。这些数据表明，多发性骨髓瘤患者化疗失败与mdr1基因表达增加以及其他基因表达增加之间存在显著关系，这些基因的产物将产生对化疗药物的额外耐药机制。
We have quantitated the levels of mRNAs in bone marrow samples from patients with multiple myeloma of the mdr1 gene (responsible for the Multidrug Resistance phenotype) and for two of the glutathione S-transferase gene, GST-2 and GST-3 (which can also inactivate a wide variety of cytotoxic drugs) and examined the relationship between the levels of expression of these genes and response to subsequent chemotherapy. From a total of 47 patients, 37 were treated with chemotherapy with 34 evaluable for response. Twenty-nine of the patients treated had not received any treatment prior to the marrow sampling while eight had previously received chemotherapy. Patients who failed to respond to initial chemotherapy had significantly higher levels of mdr1 than patients who responded (P = 0.01). In the total myeloma patient data set, mRNA levels for mdr1 and GST-2 were significantly correlated (Spearman rank correlation coefficient (r) = 0.54, P = 0.0004) as were expression levels of GST-2 with GST-3 (r = 0.43, P = 0.017). GST-3 and mdr1 levels were more weekly associated (r = 0.16, P = 0.4). These data would suggest a significant relationship between failure of chemotherapy in multiple myeloma patients and increases in expression of the mdr1 gene together with other genes whose products will generate additional mechanisms of resistance to chemotherapeutic agents.