急性白血病中耐药基因的表达

Expression of resistance genes in acute leukemia.

作者信息

Zhou D C, Hoang-Ngoc L, Delmer A, Faussat A M, Russo D, Zittoun R, Marie J P

机构信息

Laboratoire de Cinétique et de Cultures Cellulaires, Formation de Recherche Associée Claude Bernard sur le Traitement des Hémopathies Malignes, Paris, France.

出版信息

Leuk Lymphoma. 1994;13 Suppl 1:27-30. doi: 10.3109/10428199409052669.

DOI:10.3109/10428199409052669

PMID:8075575

Abstract

To evaluate the frequency and the prognostic value of different mechanisms of drug resistance in acute leukemias, we investigated the expression of mdr1 by immunocytochemistry, mRNA slot blot or RT-PCR in 182 cases of adult acute myeloid and 37 cases of adult lymphoblastic leukemia. Before treatment, 39% of de novo AML, 38% of secondary AML, and 7% of de novo ALL exhibited a high level of mdr1 mRNA. After chemotherapy, the frequency of mdr1 gene expression in ALL raised dramatically to 60% (P < 0.005), while no significant change was found for AML cases. In 91 patients treated with MDR-related drugs, mdr1 gene expression was related to the failure of chemotherapy (P < 0.0001). The overexpression of multidrug resistance-associated protein (mrp) and anionic glutathione S-transferase (GST pi) was also investigated in 38 and 61 AML patients respectively. An overexpression of mrp gene was noted in 39% of the cases. For GST pi gene, the frequency of overexpression was 28%. A positive and significative correlation was found among mdr1, mrp and GST pi genes expression.

摘要

为评估急性白血病中不同耐药机制的频率及其预后价值，我们采用免疫细胞化学、mRNA 斑点杂交或逆转录聚合酶链反应（RT-PCR）检测了182例成人急性髓系白血病及37例成人淋巴细胞白血病患者的mdr1表达情况。治疗前，39%的初治急性髓系白血病（AML）、38%的继发性AML及7%的初治急性淋巴细胞白血病（ALL）呈现高水平mdr1 mRNA。化疗后，ALL中mdr1基因表达频率显著升至60%（P < 0.005），而AML患者未见明显变化。在91例接受与多药耐药（MDR）相关药物治疗的患者中，mdr1基因表达与化疗失败相关（P < 0.0001）。我们还分别检测了38例AML患者多药耐药相关蛋白（mrp）及61例AML患者阴离子型谷胱甘肽S-转移酶（GST pi）的过表达情况。39%的病例存在mrp基因过表达。GST pi基因过表达频率为28%。mdr1、mrp及GST pi基因表达之间呈显著正相关。