Overexpression of multidrug resistance-associated protein (MRP) gene in a refractory B-cell non-Hodgkin's lymphoma

To address the clinical importance of multidrug To resistance-associated protein (MRP) expression in vivo, we describe a patient with non-Hodgkin's lymphoma (NHL) with overexpressed MRP that was refractory to treatment. The tumor section at diagnosis and lymphoma cells in the bone marrow at relapse were obtained from a 15year-old boy with B-cell type NHL. His disease progressed despite aggressive chemotherapy, and he died approximately 6 months after the diagnosis. The levels of MRP expression in the samples were determined by immunostaining, competitive reverse transcription-polymerase chain reaction (CRT-PCR) and Southern analysis. In his tumor tissue, a small number of MRP-overexpressing cells were detected by the monoclonal antibody, and they were selectively increasing in number in the bone marrow at relapse. High levels of MRP mRNA quantitated by CRT-PCR were demonstrated in his bone marrow cells. Amplification of the MRP gene was demonstrated by Southern analysis and exhibited increased copy number at the terminal stage of disease. We concluded that the overexpression of MRP might be involved, at least in part, in the clinical refractoriness of NHL in this patient and that it was mediated by amplification of the MRP gene.