Expression of the multidrug transporter P-glycoprotein and in vitro chemosensitivity: correlation with in vivo response to chemotherapy in acute myeloid leukemia.

M Chitnis, U Hegde, S Chavan, A Juvekar, S Advani
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引用次数: 11

Abstract

Thirty four patients with acute myeloid leukemia (AML) (30 de novo and 4 relapsed) were evaluated for P-glycoprotein (P-gp) expression, and in vitro chemosensitivity. The P-gp expression was evaluated by immunohistochemical method using JSB-1 monoclonal antibody and the results were visualized by peroxidase-antiperoxidase goat antimouse antibody and the in vitro chemosensitivity was measured by the semiautomated MTT colourimetric assay method. Depending upon the percent cells expressing P-gp and the intensity of P-gp staining, the samples were graded as absent, mild or strong for the relative P-gp expression, which was further correlated with the in vitro chemosensitivity and the clinical response of the tumors. Expression of P-gp was seen in 17 of the 30 de novo AML cases and all four relapse cases. Patients with no P-gp expression showed in vitro chemosensitivity while those with strong P-gp expression were resistant in vitro. Patients with mild P-gp expression showed varied chemosensitivity. P-gp expression correlated with clinical response to chemotherapy. Seven out of 11 patients with no P-gp achieved complete remission (C.R.). The other four died early in induction. Of five patients who expressed strong P-gp, four had resistant disease and the autopsy study of the remaining patient who died in induction revealed persistent disease. Of the 10 de novo AML patients who had mild P-gp expression, five achieved C.R. while one had resistant disease and four died in induction. All the four relapsed AML showed mild P-gp expression.(ABSTRACT TRUNCATED AT 250 WORDS)

多药转运蛋白p -糖蛋白的表达和体外化疗敏感性:与急性髓系白血病体内化疗反应的相关性
对34例急性髓性白血病(AML)患者(30例新发,4例复发)p -糖蛋白(P-gp)表达及体外化疗敏感性进行了评估。采用JSB-1单克隆抗体免疫组化法检测P-gp的表达,采用过氧化物酶-抗过氧化物酶山羊抗小鼠抗体检测结果,采用半自动MTT比色法检测体外化学敏感性。根据表达P-gp的细胞百分比和P-gp染色的强度,将样品分为P-gp相对表达不存在、轻度或强烈,这进一步与体外化疗敏感性和肿瘤的临床反应相关。30例AML新发病例中的17例和4例复发病例中均可见P-gp的表达。P-gp不表达的患者体外化疗敏感,P-gp表达强的患者体外耐药。P-gp轻度表达的患者表现出不同的化疗敏感性。P-gp表达与临床化疗反应相关。11例无P-gp患者中有7例达到完全缓解(C.R.)。另外四人在入职时过早死亡。在表达强烈P-gp的5名患者中,4名患者患有耐药性疾病,其余在诱导中死亡的患者的尸检研究显示疾病持续存在。在10名轻度P-gp表达的新发AML患者中,5名患者获得了C.R., 1名患者出现了耐药性,4名患者在诱导中死亡。4例复发AML均有轻度P-gp表达。(摘要删节250字)
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