Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells

Abstract

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. Cancer 1995; 76:2351–6.

Immunohistochemical expression and clinical significance of P‐glycoprotein in previously untreated extranodal NK/T‐cell lymphoma, nasal type

“…P-gp was found to be overexpressed in various types of hematological malignancies including extranodal NK/T-cell lymphoma, nasal type. Previous series identified the immunohistochemical expression of P-gp from 54 to 90% in extranodal NK/T-cell lymphoma, nasal type [15,19,20]. In our study, a high expression rate of P-gp (67%) in previously untreated patients was confirmed.…”

“…P-gp was found to be overexpressed in various hematological malignancies including NHL [13]. Multiple investigators detected highlevel expression of P-gp in normal or abnormal NK cells using different methods [14][15][16][17]. Nevertheless, convincing clinical data about correlation between P-gp expression and chemoresistance or prognosis is still very limited.…”

Current and future management of NK/T-cell lymphoma based on clinical trials

“…The ENKL tumor cells express the multidrug resistance (MDR) 1/ABCB1 gene and its product, P-glycoprotein [32][33][34]. This observation is thought to be the major reason why ENKL is resistant to CHOP or CHOP-like chemotherapies, which are comprised mainly of MDR-related agents.…”

STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK/T-cell lymphoma

“…These involve mutations of genes regulating apoptosis such as Fas and p53, [6][7][8][9][10] as well as expression of P-glycoproteins. 11 Moreover, a low expression level of the granzyme B protease inhibitor 9 was associated with a worse prognosis and cell dedifferentiation, suggesting a role for this protein in the pathophysiology of these malignancies. 5 However, the mechanisms involved in the pathogenesis and resistance to treatment still remain poorly understood, and the deep research for this special tumor has been hampered by its rarity and insufficient supply of the tumoral samples.…”