FREQUENT EXPRESSION OF P-GLYCOPROTEIN MDR1 BY NASAL T-CELL LYMPHOMA-CELLS/

Background. Lethal midline granuloma is now considered to be a maligna nt lymphoma derived from peripheral T cells or from natural killer cel ls. The therapeutic outcome of nasal T-cell lymphoma (NL) treated by c onventional chemotherapy for non-Hodgkin's lymphoma is poor, although some patients have a good response to radiotherapy. To clarify the mec hanisms of drug resistance, the expression of P-glycoprotein (P-gp)/MD R1, which is the product of the multidrug resistance (MDR) 1 gene, and MDR3 mRNA in NL cells, were examined. Methods. Ten Japanese patients with NL were studied. Nine of these patients were examined before ther apy. P-glycoprotein expression and phenotypes of lymphoma cells were e xamined by immunohistochemical staining using UIC2 as an anti-P-gp mon oclonal antibody. In one case, the Rhodamine-123 efflux test was perfo rmed. MDR1 and MDR3 mRNA were detected by reverse transcription polyme rase chain reaction. Results. Nine of the 10 patients were P-gp positi ve. In one of nine, functional P-gp expression was observed. MDR1 mRNA was detected in all seven examined patients with P-gp positive NLs, w hereas MDR3 mRNA was negative. Retrospectively, patients who received chemotherapy alone had poorer outcome than those treated by combinatio n chemotherapy after irradiation. Conclusion. The poor prognosis for p atients with NL treated with chemotherapy may be explained by P-gp exp ression of the NL calls.