Wattel E, Lepelley P, Merlat A, Sartiaux C, Bauters F, Jouet J P, Fenaux P
Service des Maladies du Sang, CHU Lille, France.
Leukemia. 1995 Nov;9(11):1870-4.
We analyzed P glycoprotein (PGP) expression and its correlation with hematological parameters and outcome in 50 cases of newly diagnosed adult acute lymphoblastic leukemia (ALL). PGP expression was evaluated by flow cytometry using MRK16 monoclonal antibody (MoAb) and/or immunocytochemistry on marrow slides, using JSB1 MoAb. Thirty-two of the 50 patients (64%) were PGP positive by at least one of the two methods, which gave concordant results in 15 of the 18 cases in which they were both used. No correlation between PGP expression and clinical and hematological parameters including WBC counts, immunophenotype and karyotype was seen, although there was a trend for more frequent CD34 expression in PGP-positive cases. All patients were treated with intensive chemotherapy. We found no difference in complete remission (CR) rate, actuarial disease-free survival and survival in PGP-positive and PGP-negative cases. Our findings suggest that the clinical significance of PGP expression is less clear in ALL than in AML. Wider use of functional techniques of evaluation of mdr1 gene expression, which assess the 'pumping' activity of PGP, and their correlation with quantitative analysis of mdr1 mRNA and protein, would probably improve knowledge of the role of PGP in ALL. Analysis of other mechanisms of drug resistance, especially multidrug resistance-associated protein (MRP) expression, would also be useful.
我们分析了50例新诊断的成年急性淋巴细胞白血病(ALL)患者中P糖蛋白(PGP)的表达情况及其与血液学参数和预后的相关性。通过使用MRK16单克隆抗体(MoAb)的流式细胞术和/或在骨髓涂片上使用JSB1 MoAb进行免疫细胞化学来评估PGP表达。50例患者中有32例(64%)通过两种方法中的至少一种检测为PGP阳性,在同时使用两种方法检测的18例患者中,有15例结果一致。尽管PGP阳性病例中CD34表达更频繁有一定趋势,但未发现PGP表达与包括白细胞计数、免疫表型和核型在内的临床和血液学参数之间存在相关性。所有患者均接受强化化疗。我们发现PGP阳性和PGP阴性病例在完全缓解(CR)率、无病生存率和总生存率方面没有差异。我们的研究结果表明,PGP表达在ALL中的临床意义不如在AML中明确。更广泛地使用评估mdr1基因表达的功能技术,该技术可评估PGP的“泵出”活性,并将其与mdr1 mRNA和蛋白的定量分析相关联,可能会增进对PGP在ALL中作用的了解。分析其他耐药机制,尤其是多药耐药相关蛋白(MRP)的表达,也将是有益的。