Association of P-glycoprotein and Bcl-2 with multi-drug resistance in chronic lymphocytic leukaemia


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Shams Ismail1, Amira Khorshed2, Nahed Abdelwahab2, Thoraya Abdelhamid2

1National Research Center, Giza, Cairo, Egypt, 2National Cancer Institute, Cairo, Egypt

Abstract

Chronic lymphocytic leukaemia (CLL) is a hematopoietic neoplasm characterized by defect in apoptosis and complicated by the progressive marrow failure, immunosuppression and increased resistance to chemotherapy. A major problem in CLL treatment is the development of resistance to chemotherapeutic agents in tumor cells. A mechanism of this multi-drug resistance (MDR) is the overexpression of MDR-1 gene which codes for P-glycoprotein (P-gp). In addition, the overexpression of B-cell lymphoma-2 (Bcl-2) gene suppresses apoptosis and acts as a mechanism of drug resistance. The aim of this study was to assess P-gp and Bcl-2 expression and their correlation with clinical features, prognosis and response to treatment in CLL patients.

This study included thirty de novo chronic lymphocytic leukaemia patients. Measurements of P-gp and Bcl-2 expression prior to and after treatment were done by flow cytometry and immunocytochemistry. By follow up, response to chemotherapy was evaluated to: complete remission, partial remission, progressive disease or stationary disease. This study revealed statistically significant correlation between P-gp expression (before and after treatment) and poor response to treatment. While for Bcl-2 expression measured by both techniques, there was a statistically significant correlation between Bcl-2 expression after treatment and poor response to treatment.

Chronic lymphocytic leukaemia (CLL) is a hematopoietic neoplasm characterized by defect in apoptosis and complicated by the progressive marrow failure, immunosuppression and increased resistance to chemotherapy. A major problem in CLL treatment is the development of resistance to chemotherapeutic agents in tumor cells. A mechanism of this multi-drug resistance (MDR) is the overexpression of MDR-1 gene which codes for P-glycoprotein (P-gp). In addition, the overexpression of B-cell lymphoma-2 (Bcl-2) gene suppresses apoptosis and acts as a mechanism of drug resistance. The aim of this study was to assess P-gp and Bcl-2 expression and their correlation with clinical features, prognosis and response to treatment in CLL patients.

This study included thirty de novo chronic lymphocytic leukaemia patients. Measurements of P-gp and Bcl-2 expression prior to and after treatment were done by flow cytometry and immunocytochemistry. By follow up, response to chemotherapy was evaluated to: complete remission, partial remission, progressive disease or stationary disease. This study revealed statistically significant correlation between P-gp expression (before and after treatment) and poor response to treatment. While for Bcl-2 expression measured by both techniques, there was a statistically significant correlation between Bcl-2 expression after treatment and poor response to treatment.