Fazlina N, Maha A, Zarina A L, Hamidah A, Zulkifli S Z, Cheong S K, Ainoon O, Jamal R, Hamidah N H
Haematology Unit, Department of Pathology, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur.
Malays J Pathol. 2008 Dec;30(2):87-93.
Multidrug resistance (MDR) is believed to be responsible for poor response of patients towards chemotherapy particularly patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The best-characterized resistance mechanism is the one mediated by permeability-glycoprotein (P-gp) encoded by MDR1 gene, which is responsible for drug efflux. We studied P-gp and multidrug resistance-associated protein 1 (MRP1) expression and functional activities in 43 newly diagnosed acute leukemia cases (19 paediatric ALL cases and 24 adult AML cases). The expression and functional activities were examined using flow cytometry and MultiDrugQuant assay kit (involving calcein AM uptake and efflux). P-gp and MRP1 expression and its functional activities were observed in 68.4% of paediatric ALL. In adult AML cases, all cases expressed MRP1 and its functional activities but only 58.3% were positive for P-gp and its functional activities. We were able to show a significant correlation between the expression of the multidrug resistant protein (P-gp and MRP1) and their functional activity in adult AML and paediatric ALL samples.
多药耐药(MDR)被认为是导致患者尤其是急性髓系白血病(AML)和急性淋巴细胞白血病(ALL)患者对化疗反应不佳的原因。最具特征的耐药机制是由MDR1基因编码的通透性糖蛋白(P-gp)介导的机制,该蛋白负责药物外排。我们研究了43例新诊断的急性白血病病例(19例儿童ALL病例和24例成人AML病例)中P-gp和多药耐药相关蛋白1(MRP1)的表达及功能活性。使用流式细胞术和多药定量检测试剂盒(包括钙黄绿素AM摄取和外排)检测表达及功能活性。在68.4%的儿童ALL病例中观察到了P-gp和MRP1的表达及其功能活性。在成人AML病例中,所有病例均表达MRP1及其功能活性,但只有58.3%的病例P-gp及其功能活性呈阳性。我们能够证明在成人AML和儿童ALL样本中,多药耐药蛋白(P-gp和MRP1)的表达与其功能活性之间存在显著相关性。