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Published on: March 26, 2018
P-glycoprotein (P-170) expression in acute leukemias
Hasan A Abd El-Ghaffar1, Doaa A Aladle, Sami E Farahat
1Faculty of Medicine, Mansoura University, Hematology Unit of Clinical Pathology Department, Mansoura, Egypt. haabd-elghaffar@man.edu.eg
Abstract:
Multidrug resistance (MDR) is still a major obstacle to chemotherapy success in acute myeloid leukemia (AML) and to a less extent acute lymphoblastic leukemia (ALL). Recent studies have shown that the expression of certain gene products mediate the development of resistance to chemotherapeutic agents. The most well characterized of these genes is the multidrug resistance gene MDR-1. This study was planned to study the expression of P-glycoprotein/170 in patients with acute leukemia and the effect of Cyclosporin A (CSA) as a modulator of P-glycoprotein functional activity. The study was carried out on 20 patients with acute leukemia (14 AML cases and 6 ALL cases). In addition, 6 normal individuals served as a reference group. Flow cytometric analysis of P-gp/170 surface expression was performed using UIC-2 MoAb together with the functional assay using Rhodamine 123 (Rh 123) and Cyclosporin A as a modulator.P-gp/170 was expressed on the leukemic cells of 37.5% of relapsed patients (40.0% of AML and 33.3% of ALL cases), whereas 27.2% of de novo patients expressed P-gp/170 (33.3% of AML cases and 0% of ALL cases). The functional activity of MDR-1 gp was 71.4% in AML and 33.3% in ALL patients compared with16.6% in normal lymphocytes. From this study, it is clear that P-gp/170 is expressed to a higher degree in leukemic cells and this is greater in relapsed compared to de novo cases and more in AML than ALL blasts. Functional activity is a more sensitive predictor of chemoresistance than P-gp/170 surface expression.
Insights
Multidrug resistance (MDR) in acute leukemia is linked to P-glycoprotein (P-gp/170) expression. Functional P-gp activity, not just surface expression, is a better indicator of chemotherapy resistance in AML and ALL patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Multidrug resistance (MDR) significantly hinders chemotherapy efficacy in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
- The MDR-1 gene product, P-glycoprotein (P-gp/170), is a key mediator of chemoresistance.
- Understanding P-gp expression and function is crucial for improving leukemia treatment outcomes.
Purpose of the Study:
- To investigate P-glycoprotein/170 expression in acute leukemia patients.
- To evaluate the impact of Cyclosporin A (CSA) on P-gp functional activity.
- To compare P-gp surface expression with functional activity as predictors of chemoresistance.
Main Methods:
- Flow cytometry was used to analyze P-gp/170 surface expression on leukemic cells from 20 acute leukemia patients (14 AML, 6 ALL) and 6 healthy controls.
- Functional P-gp activity was assessed using Rhodamine 123 (Rh 123) efflux assays, with CSA as a modulator.
- P-gp expression and functional assays were correlated with patient status (de novo vs. relapsed).
Main Results:
- P-gp/170 was expressed on leukemic cells in 37.5% of relapsed and 27.2% of de novo acute leukemia patients.
- Expression was higher in relapsed cases (40% AML, 33.3% ALL) compared to de novo cases (33.3% AML, 0% ALL).
- Functional MDR-1 P-gp activity was significantly higher in AML (71.4%) and ALL (33.3%) patients compared to normal lymphocytes (16.6%).
Conclusions:
- P-glycoprotein/170 is frequently expressed on leukemic cells, particularly in relapsed AML and ALL.
- Functional P-gp activity is a more sensitive predictor of multidrug resistance and chemoresistance than surface P-gp expression alone.
- Targeting P-gp function may offer a strategy to overcome chemotherapy resistance in acute leukemia.
