Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes
Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes
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DOI：
10.1002/(sici)1097-0215(19990812)82:4
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发表时间：
1999-08-12
影响因子：
6.4
通讯作者：
Kohno, S
中科院分区：
文献类型：
--
作者：
Ikeda, K;Oka, M;Kohno, S
成人T细胞白血病（ATL）是由人T细胞白血病病毒-1（HTLV-1）感染引起的T细胞恶性肿瘤。ATL包括4种临床类型：急性型、慢性型、郁积型和淋巴瘤型。ATL通常对常规化疗具有耐药性，预后相对较差;然而，耐药机制仍不确定。为探讨ATL的多药耐药（MDR）机制，本研究采用半定量RT-PCR和荧光素酶扫描（FACScan）技术检测了ATL患者外周血单个核细胞（PBMC）中MDR相关基因的表达和功能活性。ATL患者PBMC表达MRP、LRP和cMOAT mRNA水平与正常PBMC相似或更高。在正常对照组和ATL患者中，MDR 1 mRNA表达在本研究中未检测到。急、慢性AIL患者外周血单个核细胞MRP和LRP mRNA表达水平均明显高于正常外周血单个核细胞（p < 0.01和p < 0.05）。慢性ATL患者MRP和LRP mRNA表达水平与外周血异常淋巴细胞绝对数量呈正相关（r = 0.759，p = 0.018）。丙磺舒，MRP泵的抑制剂，显着增加钙黄绿素在3例慢性ATL患者的PBMC中的积累。我们的研究结果表明，ATL中的MRP和LRP基因经常被HTLV-1感染激活，并可能导致ATL细胞在体内的MDR。联合化疗与这些MDR基因的抑制剂可能是有希望的治疗ATL。(C)1999 Wiley-Liss，Inc.
Adult T-cell leukemia (ATL) is a T-cell malignancy caused by human T-cell-leukemia-virus-1 (HTLV-I) infection. ATL comprises 4 clinical forms: acute, chronic, smoldering and lymphoma types. ATL is usually resistant to conventional chemotherapy and has a relatively poor prognosis; however, the resistance mechanisms remain undetermined. To explore the multidrug-resistance (MDR) mechanisms of ATL, we examined the expression and functional activity of MDR-related genes in peripheral-blood mononuclear cells (PBMC) from ATL patients by semi-quantitative RT-PCR and FACScan with calcein-AM. PBMC from ATL patients expressed similar or higher levels of MRP, LRP and cMOAT mRNAs, as compared with normal PBMC. In normal controls and ATL patients, MDR1 mRNA expression was undetectable in this study. PBMC from acute and chronic AIL patients expressed significantly higher levels of MRP and LRP mRNA than did normal PBMC (p < 0.01 and p < 0.05 respectively). In chronic ATL, positive correlations were apparent between levels of MRP and LRP mRNA expression (r = 0.759, p = 0.018), and between each mRNA level and the absolute number of abnormal lymphocytes in peripheral blood. Probenecid, an inhibitor of the MRP pump, significantly increased the accumulation of calcein in PBMC from 3 chronic ATL patients. Our findings suggest that the MRP and LRP genes in ATL ave often activated by HTLV-I infection and may confer MDR of ATL cells in vivo. Combined chemotherapy with inhibitors of these MDR genes may be promising in the treatment of ATL. (C) 1999 Wiley-Liss, Inc.