The Experimental Foundational Study Of Multidrug Resistance In Non-Hodgkin's Lymphoma

Objective To explore the correlation of clinical general parameters and chemotherapy efficacy with the expression of P-glycoprotein(P-gp)/mdr1mRNA,multidrug resistance-associated protein(MRP)and lung resistance protein(LRP)in untreated non-Hodgkin's lymphoma.Methods(1)To select 13 examples of PLN as control group,and to select 41 samples of NHL as test group.(2)All samples' fresh lymph nodes tissue were obtained from lymph nodes biopsy or needle puncture and prepared suspended single cells by machine separation.(3)We developed multiparameter flow cytometric assay to quantify expression of these multidrug resistance(MDR)proteins in lymph node viable blasts and reverse transcriptasepolymerase chain reaction(RT-PCR)method to semi-quantitate mdr1mRNA of 41 non-Hodgkin's lymphomas.(4)x~2 analysis and Spearman analysis were used to study the correlation of the multidrug resistance proteins with general clinical parameters and treatment outcome.Results(1)Frequencies of the MDR proteins was:P-gp+19.5%(8/41),MRP+17.1% (7/41),LRP+36.6%(15/41),mdr1mRNA:26.8%(22/41).(2)P-gp and LRP level in NHL were higher than the control group,but MRP wasn't.P-gp overexpression was significantly associated with mdr1mRNA(r=0.396,P=0.01).However,no correlation showed among P-gp,MRP and LRP.(3)Patients with P-gp expression had a poor outcome of chemotherapy than those without P-gp(P=0.005).P-gp expression was associated with higher clinical stage(P=0.046),elevated serum lactate dehydrogenase levels(P=0.032)and not associated with higher malignant degree (P=0.298).MRP had no impact on the outcome of chemotherapy(P=0.212),and wasn't associated with higher clinical stage(P=0.369),elevated LDH(P=0.762)and higher malignant degree(P=0.451).Patients with LRP expression had a poor outcome of chemotherapy than those without LRP(P=0.012).LRP expression was associated with higher clinical stage(P=0.0019), elevated LDH(P=0.02)and higher malignant degree(P=0.01).Conclusions These data suggest that P-gp and LRP expression but not MRP1 expression are important mechanism of drug resistance associated with worse clinical outcome in previously untreated NHL.