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急性髓系白血病原始细胞在诊断时的P-糖蛋白表达可预测化疗反应和生存期。

P-glycoprotein expression on acute myeloid leukaemia blast cells at diagnosis predicts response to chemotherapy and survival.

作者信息

Wood P, Burgess R, MacGregor A, Yin J A

机构信息

University Department of Haematology, Manchester Royal Infirmary.

出版信息

Br J Haematol. 1994 Jul;87(3):509-14. doi: 10.1111/j.1365-2141.1994.tb08305.x.

Abstract

P-glycoprotein (Pgp) expression, which is associated with the multi-drug resistance (MDR) phenotype, has been reported to be a useful predictor of treatment outcome in acute leukaemia. We have examined the expression of Pgp on acute myeloid leukaemia (AML) cells in 54 newly diagnosed patients, using a novel streptavidin-biotin complex (ABC) technique. 55% of patients at diagnosis were positive for Pgp with JSB-1, a monoclonal antibody that binds to an internal epitope of Pgp. All patients received intensive induction chemotherapy. Post-remission treatment consisted of further chemotherapy +/- bone marrow transplantation. Complete remission (CR) rates were significantly lower in the Pgp positive group than in the Pgp negative group (60% v 92%; P = 0.02). The overall survival for Pgp-positive patients was significantly shorter (329 v 534d, P = 0.004), disease-free survival was also reduced but the difference was not statistically significant (median 277 v 522d, P = 0.16). In this study CD34 expression was not predictive of response to chemotherapy nor was it associated with Pgp expression. Our results confirm the prognostic value of Pgp expression in AML at diagnosis and we suggest that Pgp could be a useful therapeutic target for reversing multi-drug resistance. Furthermore, our simple and sensitive method of detecting Pgp should enable widespread testing to be performed.

摘要

据报道,与多药耐药(MDR)表型相关的P-糖蛋白(Pgp)表达可作为急性白血病治疗结果的有用预测指标。我们采用一种新型的链霉亲和素-生物素复合物(ABC)技术,检测了54例新诊断急性髓系白血病(AML)患者AML细胞上Pgp的表达情况。诊断时,55%的患者使用能与Pgp内部表位结合的单克隆抗体JSB-1检测Pgp呈阳性。所有患者均接受了强化诱导化疗。缓解后治疗包括进一步化疗和/或骨髓移植。Pgp阳性组的完全缓解(CR)率显著低于Pgp阴性组(60%对92%;P = 0.02)。Pgp阳性患者的总生存期显著缩短(329天对534天,P = 0.004),无病生存期也缩短,但差异无统计学意义(中位数277天对522天,P = 0.16)。在本研究中,CD34表达既不能预测化疗反应,也与Pgp表达无关。我们的结果证实了诊断时Pgp表达在AML中的预后价值,并且我们认为Pgp可能是逆转多药耐药的一个有用治疗靶点。此外,我们检测Pgp的简单且灵敏的方法应能使广泛检测得以开展。

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