Korean J Hematol.  1999 Aug;34(3):416-427.

Clinical Usefulness of Flow Cytometric Measurement of P-glycoprotein, Glutathione S-Transferase pie and Topoisomerase II alpha Expression in Adult Acute Myelogenous Leukemia

• Lee JN
• Lee EY
• Cho GJ

Abstract

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-transferasepie (GSTpie) is related to clinical outcome following chemotherapy. Topoisomerase IIalpha (topo IIalpha) is a major target of anthracyclines for the treatment of leukemia.
METHODS
To evaluate the relation of PGP, GSTpie and topo IIalpha expression to treatment outcome, PGP, GSTpie and topo IIalpha expression were analysed by flow cytometry using mono clonal antibodies (anti-JSB1, anti-GSTpie and anti-topo IIalpha) 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 GST pie 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 GSTpie (40.0 vs 84.6%, P=0.011; 115 vs 343 days, P=0.021). The frequency of patients with high expression of topo IIalpha is 78.8% (26/33) and treatment outcome was not related to topo IIalpha expression. In multivariate analysis with age, WBC count, PGP and GSTpie, PGP expression was an independent prognostic factor for treatment outcome.
CONCLUSION
The flow cytometric measurement of PGP and GSTpie expression can be useful for the prediction of treament outcome following chemotherapy and PGP can be used as aprognostic factor in AML.

Keyword

Acute myelogenous leukemia; Multidrug resistance; Flow cytometry, P-glycoprotein; Glutathione S-transferase pie; Topoisomerase IIalpha

MeSH Terms

Adult*
Anthracyclines
Antibodies
Cytosol
DNA Topoisomerases, Type II*
Drug Resistance
Drug Resistance, Multiple
Drug Therapy
Flow Cytometry
Glutathione S-Transferase pi*
Glutathione Transferase*
Glutathione*
Humans
Leukemia
Leukemia, Myeloid, Acute*
Multivariate Analysis
P-Glycoprotein*
Treatment Outcome
Anthracyclines
Antibodies
DNA Topoisomerases, Type II
Glutathione
Glutathione S-Transferase pi
Glutathione Transferase
P-Glycoprotein