BACKGROUND: Lethal midline granuloma is now considered to be a malignant lymphoma derived from peripheral T cells or from natural killer cells. The therapeutic outcome of nasal T-cell lymphoma (NL) treated by conventional chemotherapy for non-Hodgkin's lymphoma is poor, although some patients have a good response to radiotherapy. To clarify the mechanisms of drug resistance, the expression of P-glycoprotein (P-gp)/MDR1, 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 therapy. P-glycoprotein expression and phenotypes of lymphoma cells were examined by immunohistochemical staining using UIC2 as an anti-P-gp monoclonal antibody. In one case, the Rhodamine-123 efflux test was performed. MDR1 and MDR3 mRNA were detected by reverse transcription polymerase chain reaction. RESULTS: Nine of the 10 patients were P-gp positive. In one of nine, functional P-gp expression was observed. MDR1 mRNA was detected in all seven examined patients with P-gp positive NLs, whereas MDR3 mRNA was negative. Retrospectively, patients who received chemotherapy alone had poorer outcome than those treated by combination chemotherapy after irradiation. CONCLUSION: The poor prognosis for patients with NL treated with chemotherapy may be explained by P-gp expression of the NL cells.
BACKGROUND: Lethal midline granuloma is now considered to be a malignant lymphoma derived from peripheral T cells or from natural killer cells. The therapeutic outcome of nasal T-cell lymphoma (NL) treated by conventional chemotherapy for non-Hodgkin's lymphoma is poor, although some patients have a good response to radiotherapy. To clarify the mechanisms of drug resistance, the expression of P-glycoprotein (P-gp)/MDR1, 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 therapy. P-glycoprotein expression and phenotypes of lymphoma cells were examined by immunohistochemical staining using UIC2 as an anti-P-gp monoclonal antibody. In one case, the Rhodamine-123 efflux test was performed. MDR1 and MDR3 mRNA were detected by reverse transcription polymerase chain reaction. RESULTS: Nine of the 10 patients were P-gp positive. In one of nine, functional P-gp expression was observed. MDR1 mRNA was detected in all seven examined patients with P-gp positive NLs, whereas MDR3 mRNA was negative. Retrospectively, patients who received chemotherapy alone had poorer outcome than those treated by combination chemotherapy after irradiation. CONCLUSION: The poor prognosis for patients with NL treated with chemotherapy may be explained by P-gp expression of the NL cells.
Authors: Jonathan E Brammer; Dai Chihara; L Michelle Poon; Paolo Caimi; Marcos de Lima; Celina Ledesma; Gabriela Rondon; Stefan O Ciurea; Yago Nieto; Michelle Fanale; Bouthaina Dabaja; Richard T Maziarz; Richard E Champlin; Chitra Hosing; Yasuhiro Oki Journal: Clin Lymphoma Myeloma Leuk Date: 2017-10-12