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多药耐药标志物P-糖蛋白在B细胞慢性淋巴细胞白血病中的常见表达及其与体外耐药性的相关性

Common expression of the multidrug resistance marker P-glycoprotein in B-cell chronic lymphocytic leukaemia and correlation with in vitro drug resistance.

作者信息

Sparrow R L, Hall F J, Siregar H, Van der Weyden M B

机构信息

Pathology Service, Alfred Hospital, Prahran, Victoria, Australia.

出版信息

Leuk Res. 1993 Nov;17(11):941-7. doi: 10.1016/0145-2126(93)90041-i.

DOI:10.1016/0145-2126(93)90041-i
PMID:7901453
Abstract

The expression of P-glycoprotein (Pgp), which is associated with multidrug resistance (MDR), was investigated in 20 B-cell chronic lymphocytic leukaemia (B-CLL) patients by flow cytometry using two Pgp-specific monoclonal antibodies (mAb), MRK-16 which recognizes an extracellular epitope, and JSB-1 which recognizes an intracellular epitope. Sixteen (80%) patients were positive with MRK-16 whereas all patients were positive with JSB-1. The proportion of Pgp-positive lymphocytes from each patient sample varied from 2-94% for MRK-16 and 20-93% for JSB-1. There was no correlation between the level of positivity and disease stage or treatment history. In vitro drug resistance to vincristine (VCR) and doxorubicin (DOX) was determined by the colorimetric MTT assay. All patients were resistant to one or both drugs being consistent with the expression of Pgp. There was no correlation between the level of resistance and disease stage or drug treatment. We investigated the expression of Pgp in the normal counterpart of the B-CLL cells, CD5+CD19+ B-lymphocytes. A minor subpopulation (3%) of CD5+CD19+ lymphocytes isolated from normal controls expressed Pgp suggesting that these cells may be the potential precursors to the B-CLL cell. We conclude that Pgp expression and drug resistance are inherent characteristics of the B-CLL lymphocyte.

摘要

通过流式细胞术,使用两种P-糖蛋白(Pgp)特异性单克隆抗体(mAb),即识别细胞外表位的MRK-16和识别细胞内表位的JSB-1,对20例B细胞慢性淋巴细胞白血病(B-CLL)患者中与多药耐药性(MDR)相关的P-糖蛋白(Pgp)表达进行了研究。16例(80%)患者的MRK-16检测呈阳性,而所有患者的JSB-1检测均呈阳性。每个患者样本中Pgp阳性淋巴细胞的比例,MRK-16检测为2%至94%,JSB-1检测为20%至93%。阳性水平与疾病分期或治疗史之间无相关性。通过比色MTT法测定了对长春新碱(VCR)和阿霉素(DOX)的体外耐药性。所有患者对一种或两种药物耐药,这与Pgp的表达一致。耐药水平与疾病分期或药物治疗之间无相关性。我们研究了B-CLL细胞的正常对应物CD5+CD19+B淋巴细胞中Pgp的表达。从正常对照中分离出的CD5+CD19+淋巴细胞的一小部分亚群(3%)表达Pgp,提示这些细胞可能是B-CLL细胞的潜在前体。我们得出结论,Pgp表达和耐药性是B-CLL淋巴细胞的固有特征。

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