BACKGROUND: P-glycoprotein (PGP) is capable of expelling cytotoxic drugs from cytosol and the overexpression mediates drug resistance. However not all resistant leukemic cells express PGP. High expression of glutathione S-transferase π (GSTπ) is related to clinical outcome following chemotherapy. Topoisomerase IIα (topo IIα) is a major target of anthracyclines for the treatment of leukemia.
METHODS: To evaluate the relation of PGP, GSTπ and topo IIα expression to treatment outcome, PGP, GSTπ and topo IIα expression were analysed by flow cytometry using monoclonal antibodies (anti-JSB1, anti-GSTπ and anti-topo IIα) in 33 cases of de novo acute myelogenous leukemia.
RESULTS: In patients with AML, the frequency of patients with high expression of PGP was 57.6% (19/33). The complete remission (CR) rate and mean survival duration were significantly different between patients with high expression and those with low expression of PGP (31.6 vs 92.9%, P=0.001; 83 vs 341 days, p=0.011). The frequency of patients with high expression of GSTπ was 60.6% (20/33). The CR rate and mean survival duration were significantly different between patients with high expression and
those with low expression of GSTπ (40.0 vs 84.6%, P=0.011: 115 vs 343 days, P=0.021). The frequency of patients with high expression of topo IIα is 78.8% (26/33) and treatment outcome was not related to topo IIα expression. In multivariate analysis with age, WBC count, PGP and GSTπ, PGP expression was an independent prognostic factor for treatment outcome.
CONCLUSION: The flow cytometric measurement of PGP and GSTπ expression can be useful for the prediction of treatment outcome following chemotherapy and PGP can be used as aprognostic factor in AML.

Keywords: Acute myelogenous leukemia, Multidrug resistance, Flow cytometry, P-glycoprotein, Glutathione S-transferase π, Topoisomerase IIα