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

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.