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

Abstract

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. Key words: Lymphoma, non-Hodgkin; Multidrug resistance associated proteins; P-glycoprotein