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目的:研究急性白血病(AL)多药耐药相关蛋白(MRP)基因表达与临床耐药的关系。方法:应用半定量逆转录-聚合酶链反应,检测了65例AL患者骨髓和15名正常人外周血单个核细胞中MRP基因的表达。以MRP/β2微球蛋白(β2M)评价MRP的表达水平,将MRP/β2M≥0.3表示为MRP阳性。结果:复发难治组MRP的平均表达水平及阳性率最高,与正常对照组、初治组、长期生存组的MRP平均表达水平及阳性率相比均有显著差异(P<0.05),而长期生存组与正常对照组之间无统计学差异。初治组MRP阳性病例与MRP阴性病例的首次完全缓解率(分别为25%和84%)之间有显著差异。MRP表达水平在FAB各亚型间略有差异。同时检测了65例AL患者mdr-1基因的表达,发现临床耐药组MRP和mdr-1的平均表达水平及阳性率均明显高于临床非耐药组,MRP和mdr-1基因的表达水平之间无相关性(rs=0.1683)。结论:MRP基因过度表达可导致临床耐药,是预后的重要不利因素。
Objective: To study the relationship between gene expression of multidrug resistance-associated protein (MRP) and clinical drug resistance in acute leukemia (AL). METHODS: Semiquantitative reverse transcription-polymerase chain reaction was used to detect the expression of MRP gene in peripheral blood mononuclear cells from 65 patients with AL and 15 normal controls. The expression level of MRP was evaluated with MRP/β2 microglobulin (β2M), and MRP/β2M≥0.3 was expressed as MRP positive. Results: The average expression level and positive rate of MRP in the relapsed and refractory group were the highest, compared with the average expression level and positive rate of MRP in the normal control group, the untreated group, and the long-term survival group (P<0.05). There was no statistical difference between the long-term survival group and the normal control group. There was a significant difference between the initial complete remission rate (25% and 84%, respectively) of the MRP-positive and MRP-negative cases in the untreated group. MRP expression levels differ slightly between FAB subtypes. At the same time, the expression of mdr-1 gene was detected in 65 AL patients. The mean expression level and positive rate of MRP-1 and mdr-1 in the clinical drug resistance group were significantly higher than those in the clinical non-resistance group, and the expression levels of MRP and mdr-1 genes were found. There is no correlation (rs=0.1683). Conclusion: Overexpression of MRP gene can lead to clinical drug resistance, which is an important adverse factor for prognosis.