Changed expression and function of P-gp in peripheral blood CD56 ⁺ cells predicting chemoresistance in non-Hodgkin lymphoma patients

Abstract

BACKGROUND: Multi-drug resistance (MDR) remains to be a major obstacle toward successful chemotherapy of NHL patients. P-glycoprotein (P-gp), a classical protein associated with MDR, has been observed in peripheral blood CD56 ⁺ cells with high expression and activity. While the CD56 expression has been shown to be associated with a highly aggressive clinical course and chemoresistance in Non-Hodgkin lymphoma (NHL).

OBJECTIVE: To investigate the role of peripheral blood CD56 ⁺ cells in predicting the MDR of NHL by determining the P-gp expression and function of the CD56 ⁺ cells.

METHODS: The expression levels of MDR1 mRNA and MRP1 mRNA and the function of P-gp in the CD56 ⁺ cells were evaluated by RT-qPCR and flow cytometry respectively in 52 chemoresistant and 47 chemosensitive NHL patients and 48 healthy donors.

RESULTS: In the chemoresistant group, the mRNA expression level of MDR1 elevated about 2∼ 8 fold (mean = 4.24 ± 0.17) in the purified CD56^+ cells, whereas there was only about 1∼ 2.5 fold (mean = 1.69 ± 0.41) elevated for the MRP1 gene. The mean fold change of MDR1 mRNA expression in the chemoresistant group significantly increased when compared with that in the chemosensitive patients (P < 0.001). The mean fluorescence intensities (MFI) in the total gated CD56^{ + } and Rho123 double positive cells in the chemoresistant patients statistically decreased compared with that in the healthy controls and the chemosensitive NHL patients (P < 0.01).

CONCLUSIONS: Determining the P-gp expression and function of the peripheral blood CD56^{ + } cells may help predict the MDR of NHL, thus has profound guiding significance for NHL treatment.

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