非霍奇金淋巴瘤多药耐药蛋白在淋巴结与骨髓液中表达的实验研究  

Experimental study Of multi-drug resistance protein from bone marrow and lymph node in non- Hodgkin lymphoma

作　　者：苏丽萍[1] 马莉[1] 李乐 王列样[1] 赵瑾[1] 

机构地区：[1]山西省肿瘤医院血液科,太原030013 [2]山西省运城市中心医院风湿免疫科

出　　处：《白血病．淋巴瘤》2010年第12期742-745,共4页Journal of Leukemia & Lymphoma

基　　金：基金项目：山西省卫生厅科技攻关计划（200531）

摘　　要：目的 探讨初发非霍奇金淋巴瘤（NHL）骨髓液和淋巴结活组织两种标本中多药耐药蛋白的表达及临床价值评估.方法 采用流式细胞术（FCM）活细胞免疫荧光法检测41例初治NHL淋巴结活组织中和37例骨髓液中瘤细胞多药耐药蛋白及反转录-聚合酶链反应（RT-PCR）半定量检测mdr-1mRNA的表达,分析其与临床分期、恶性分级、乳酸脱氢酶（LDH）异常增高等的相关性.结果 两种标本中三种耐药基因单独及联合过度表达率无明显差异;淋巴结组织中,P-gp阳性表达在Ⅰ～Ⅱ期和Ⅲ～Ⅳ期之间有差别（P=0.046）,与LDH异常增高相关（P＜0.05）,与恶性度分级无关（P＞0.1）;肺耐药蛋白（LRP）与三者都存在明显相关（P＜0.05）.而骨髓液中仅LRP与恶性分级和LDH异常增高明显相关（P=0.01）,并未显示P-gp表达在不同分期的差异性;淋巴结中P-gp（＋）的CR率低于P-gp（-）（37.5%比84.8%）（P＜0.01）;LRP（＋）与LRP（-）的CR之间亦存在差别（53.3%比88.5%）（P＜0.01）.结论 用淋巴结活组织进行耐药蛋白检测比骨髓检测能提供更准确的临床信息,且在肿瘤尚未发生骨髓转移时,取淋巴组织亦能进行耐药蛋白检测,及早指导临床治疗及预后.Objective To compare bone marrow and lymph node biopsy specimens of two kinds of multidrug resistance （MDR） proteins expression and clinical significance in untreated non-Hodgkin lymphoma.Methods We developed multiparameter flow cytometric assay to quantify expression of these multidrug resistance （MDR） proteins in lymph node viable blasts and reverse transcriptase-polymerase chain reaction （RT-PCR） method to semi-quantitate mdrl mRNA of non-Hodgkin lymphomas, including 41 lymph node and 37 bone marrow, and further study of the correlation of the multidrug resistance proteins with general clinical parameters and treatment outcome. Results In two kinds of samples P-gp, MRP and LRP over-expression of three kinds of drug-resistant gene and frequencies are very low. Patients with P-gp expression had a poor outcome of chemotherapy than those without P-gp （P 〈0.05）, Patients with LRP expression had poor outcome of chemotherapy than those without LRP （P 〈0.01）. In the lymph node, P-gp expression was associated with higher clinical stage （P = 0.046）, elevated serum lactate dehydrogenase levels （P 〈0.05）. MRP wasn＇ t associated with higher clinical stage （P =0.369）, elevated LDH （P =0.762） and higher malignant degree（P =0.214）. LRP expression was associated with higher clinical stage, elevated LDH and higher malignant degree （P 〈0.05）. And in the bone marrow, LRP expression was associated with elevated LDH （P =0.003）, but the others have no differences. Conclusion These data suggest that P-gp and LRP expression are important mechanism of drug resistance associated with worse clinical outcome in previously untreated NHL. The use oflymph node biopsy to detect drug-resistant protein can provide more accurate clinical information than that of bone marrow.

关 键 词：淋巴瘤 非霍奇金 多药耐药相关蛋白质类 P-糖蛋白 

分 类 号：R733[医药卫生—肿瘤]