Ak Ylknur, Demirel Gülcihan, Gülbas Zafer
Departments of Nuclear Medicine, Osmangazi University Medical Faculty, 26480 Eskişehir, Turkey.
Nucl Med Commun. 2007 Jul;28(7):541-6. doi: 10.1097/MNM.0b013e328194f1cd.
Chemotherapy failure linked to multidrug-resistance (MDR) plays an important role in many cancer types, including leukaemia. It is believed that overexpression of some of membrane or intracellular proteins confers the MDR phenotype to cancer cells. (99m)Tc-sestamibi (MIBI) is a transport substrate for the Pgp pump. We assessed the bone marrow uptake of (99m)Tc-MIBI and its correlation with messenger RNA (mRNA) levels of MDR1, multidrug-resistance associated protein-1 (MRP1) and lung resistance protein (LRP) in acute leukaemia.
A total of 26 patients (age range 17-72 years; mean age 51.88+/-2.52 years) with newly diagnosed acute leukaemia were included in the study. The expression of MDR1, MRP1 and LRP on mRNA levels were assessed by quantitative RT-PCR in the blast cells. The MIBI uptake in the bone marrow was evaluated using a quantitative scoring system with determination of the tumour-to-background ratios for the bone marrow areas. The correlation between the quantitative RT-PCR results and MIBI uptake was analysed by using Spearman's rank correlation coefficients with two-tailed test of significance.
There was an inverse relationship between (99m)Tc-MIBI uptake of bone marrow and both mRNA levels of MDR1 and MRP1 (P=0.000, r= -0.733 and P=0.001, r= -0.610, respectively). No correlation was found between MIBI uptake and mRNA levels of LRP.
Increased expression of MDR1 and MRP1 correlates with a low accumulation of (99m)Tc-MIBI in bone marrow areas in patients with acute leukaemia. (99m)Tc-MIBI bone marrow scintigraphy can identify the MDR1 and MRP1 phenotype, but not LRP, in patients with acute leukaemia.
与多药耐药（MDR）相关的化疗失败在包括白血病在内的多种癌症类型中起着重要作用。据信，某些膜蛋白或细胞内蛋白的过表达赋予癌细胞MDR表型。（99m）锝-甲氧基异丁基异腈（MIBI）是Pgp泵的转运底物。我们评估了急性白血病患者骨髓对（99m）Tc-MIBI的摄取及其与多药耐药基因1（MDR1）、多药耐药相关蛋白1（MRP1）和肺耐药蛋白（LRP）信使核糖核酸（mRNA）水平的相关性。
本研究共纳入26例新诊断的急性白血病患者（年龄范围17 - 72岁；平均年龄51.88±2.52岁）。通过定量逆转录聚合酶链反应（RT-PCR）评估原始细胞中MDR1、MRP1和LRP在mRNA水平的表达。使用定量评分系统评估骨髓中MIBI的摄取情况，并测定骨髓区域的肿瘤与本底比值。采用Spearman等级相关系数和双侧显著性检验分析定量RT-PCR结果与MIBI摄取之间的相关性。
骨髓对（99m）Tc-MIBI的摄取与MDR1和MRP1的mRNA水平均呈负相关（分别为P = 0.000，r = -0.733和P = 0.001，r = -0.610）。未发现MIBI摄取与LRP的mRNA水平之间存在相关性。
急性白血病患者中，MDR1和MRP1表达增加与骨髓区域（99m）Tc-MIBI摄取低相关。（99m）Tc-MIBI骨髓闪烁显像可识别急性白血病患者的MDR1和MRP1表型，但不能识别LRP表型。
