Beck J, Niethammer D, Gekeler V
Universitäts-Kinderklinik, Abteilung Pädiatrische Hämatologie und Onkologie, Tübingen, Germany.
Cancer Lett. 1994 Oct 28;86(1):135-42. doi: 10.1016/0304-3835(94)90190-2.
Fifteen samples from 11 patients suffering from chronic lymphocytic leukaemia (CLL; 5 untreated, 6 chemotherapeutically treated) were analysed for their individual gene expression of the multidrug resistance (MDR) associated genes encoding mdr1/P-glycoprotein, mrp, and topoisomerase II alpha/beta-isoenzymes by a complementary DNA polymerase chain reaction (cDNA-PCR) approach. The expression of glyceraldehyde-3-phosphate dehydrogenase (gapdh) served as standard. Thereby, we generally found high mdr1- and mrp-, but low topoisomerase II alpha-mRNA levels. While mdr1 levels of the CLL samples were mostly found to be in the range of values measured in the T-lymphoblastoid, P-glycoprotein MDR cell line CCRF VCR 100, mrp levels were usually found to be 2-4-fold higher compared therewith. This might represent a multifactorial MDR in CLL. In contrast to the low or even absent topoisomerase II alpha gene expression, however, the expression of the topoisomerase II beta gene was generally high in the CLL lymphocytes exceeding the value observed in the cell line CCRF VCR 100 up to 5-fold. mdr1 gene expression correlated significantly with mrp gene expression in samples from patients having received chemotherapy (rs = 0.5833, P < 0.05, n = 10). In two patients the follow-up analysis revealed combined increases in mdr1- and mrp-gene expression levels in the course of the disease.
采用互补DNA聚合酶链反应（cDNA-PCR）方法，对11例慢性淋巴细胞白血病（CLL；5例未治疗，6例接受化疗）患者的15个样本进行分析，检测其多药耐药（MDR）相关基因mdr1/P-糖蛋白、多药耐药相关蛋白（mrp）以及拓扑异构酶IIα/β同工酶的个体基因表达。以甘油醛-3-磷酸脱氢酶（gapdh）的表达作为标准。由此，我们总体上发现mdr1和mrp基因表达水平较高，但拓扑异构酶IIα的mRNA水平较低。虽然CLL样本的mdr1水平大多处于在T淋巴母细胞性P-糖蛋白MDR细胞系CCRF VCR 100中测得的值范围内，但mrp水平通常比其高2至4倍。这可能代表CLL中的多因素MDR。然而，与拓扑异构酶IIα基因表达低甚至缺失相反，CLL淋巴细胞中拓扑异构酶IIβ基因的表达通常较高，超过在细胞系CCRF VCR 100中观察到的值达5倍。在接受化疗患者的样本中，mdr1基因表达与mrp基因表达显著相关（rs = 0.5833，P < 0.05，n = 10）。在两名患者中，随访分析显示在疾病过程中mdr1和mrp基因表达水平联合升高。
