Filipits M, Suchomel R W, Zöchbauer S, Brunner R, Lechner K, Pirker R
Divisions of Oncology and Hematology, Department of Internal Medicine I, University of Vienna Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Clin Cancer Res. 1997 Aug;3(8):1419-25.
Drug resistance remains a major problem in the treatment of patients with acute myeloid leukemia (AML). Expression of the MDR1 gene in leukemic cells was shown previously to be associated with worse clinical outcome of the patients. The multidrug resistance-associated protein (MRP) has been shown recently to be another protein causing the multidrug resistance phenotype in cell lines, but its impact on clinical outcome in patients with AML remains to be proven. To determine the clinical significance of MRP in patients with de novo AML, we have studied the MRP expression in leukemic cells and its association with both response to induction chemotherapy and survival of the patients. MRP gene expression was determined by immuno-cytochemistry (n = 80) by means of the monoclonal antibodies QCRL-1 and QCRL-3. MRP expression was low, intermediate, and high in 19, 55, and 26% of the patients, respectively. High MRP expression was independent of age and sex of the patients, WBC count, and percentage of blasts. However, high MRP expression was more frequent in the FAB M5 subtype as compared to the other subtypes. MRP expression had no impact on clinical outcome. The complete remission rates were 65, 68, and 63% for patients with low, intermediate, and high expression, respectively. Overall survival was also independent of MRP expression. In contrast, patients with P-glycoprotein-positive AML had lower complete remission rates and shorter durations of survival. These data indicate that MRP is expressed in patients with de novo AML but, in contrast to P-glycoprotein, does not predict for outcome of induction chemotherapy or survival.
耐药性仍然是急性髓系白血病（AML）患者治疗中的一个主要问题。先前已表明白血病细胞中MDR1基因的表达与患者较差的临床结局相关。最近已表明多药耐药相关蛋白（MRP）是另一种在细胞系中导致多药耐药表型的蛋白，但其对AML患者临床结局的影响仍有待证实。为了确定MRP在初治AML患者中的临床意义，我们研究了白血病细胞中MRP的表达及其与诱导化疗反应和患者生存的关系。通过单克隆抗体QCRL-1和QCRL-3，采用免疫细胞化学方法（n = 80）测定MRP基因表达。MRP表达低、中、高的患者分别占19%、55%和26%。MRP高表达与患者的年龄、性别、白细胞计数和原始细胞百分比无关。然而，与其他亚型相比，FAB M5亚型中MRP高表达更为常见。MRP表达对临床结局没有影响。低、中、高表达患者的完全缓解率分别为65%、68%和63%。总生存期也与MRP表达无关。相比之下，P-糖蛋白阳性的AML患者完全缓解率较低，生存期较短。这些数据表明，MRP在初治AML患者中表达，但与P-糖蛋白不同，它不能预测诱导化疗的结局或生存期。
