P-Glycoprotein (P-170) expression in acute leukemias

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 with 16.6% 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.

Keywords:

• P-GLYCOPROTEIN (P-170)
• ACUTE LEUKEMIAS
• CHEMO-RESISTANCE