High functional P-glycoprotein activity is more often present in T-cell acute lymphoblastic leukaemic cells in adults than in children
High functional P-glycoprotein activity is more often present in T-cell acute lymphoblastic leukaemic cells in adults than in children
复制标题
DOI：
10.1080/1042819021000040288
复制
发表时间：
2003-01-01
影响因子：
2.6
通讯作者：
Kamps, WA
中科院分区：
文献类型：
--
作者：
Plasschaert, SLA;Vellenga, E;Kamps, WA
儿童急性淋巴细胞性白血病(ALL)与成人急性淋巴细胞白血病(ALL)的预后有明显差异。为了明确多药耐药(MDR)基因是否参与了这种分化，采用RT-PCR(MDR-1、MRP1、MRP2、MRP3)和流式细胞仪(P-gp和MRP)检测P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP)的表达和功能活性。患者样本来自36名初发ALL儿童和35名成人。在这些患者中，38例表现为T系，33例表现为B系免疫表型。在样品中观察到P-gp活性(0.8-4.9)和MRP活性(1.1-13.9)有很大的变异性。P-gp活性高的T-ALL患者多为成人(89%)。MDR-1mRNA表达与P-gp活性呈弱相关。而MRP活性与MRP1、MRP2、MRP3mRNA表达无相关性。在T-ALL中，随着P-gp活性的增加，总体生存率和无事件生存率更差。P-gp活性对B系ALL的预后无影响。此外，高MRP活性并不影响T系或B系ALL的治疗结果。多因素COX回归分析显示，P-gp活性是影响T-ALL患者总生存率的唯一不良预后因素。总之，这项研究证实了P-gp活性在T-ALL中的预后相关性。由于P-gp活性高的患者多为成人，P-gp可能是成人T-ALL预后不良的原因之一。
There is a distinct difference in prognosis between childhood versus adult acute lymphoblastic leukaemia (ALL). To define whether multidrug resistance (MDR) genes might contribute to this distinction, the expression and functional activity of P-glycoprotein (P-gp) and MDR associated proteins (MRP) were determined with RT-PCR (MDR-1, MRP1, MRP2, MRP3) and flow cytometry (P-gp and MRP). Patient samples were obtained from 36 children and 35 adults with de novo ALL. Of these patients, 38 showed a T-lineage and 33 showed a B-lineage immunophenotype. In the samples, large variability in P-gp activity (0.8-4.9) and MRP activity (1.1-13.9) was observed. Most T-ALL patients with high P-gp activity were adults (89%). The mRNA expression of MDR-1 correlated weakly with P-gp activity. In contrast, MRP activity did not correlate with the mRNA expression of MRP1, MRP2 and MRP3. In T-ALL, a worse overall survival and event-free survival was observed with increasing P-gp activity. P-gp activity had no prognostic impact in B-lineage ALL. In addition, high MRP activity did not influence treatment outcome in either T- or B-lineage ALL. Multivariate Cox regression analysis, showed P-gp activity to be the only unfavourable prognostic factor for overall survival in T-ALL. In conclusion, this study demonstrates the prognostic relevance of P-gp activity in T-ALL. Since the majority of the patients with high P-gp activity were adults, P-gp might contribute to the poor prognosis of adult T-ALL.