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Multidrug resistance (MDR) gene expression in acute non lymphoblastic leukemia: sequential analysis
J P Marie1, O Legrand, D Russo
1Laboratoire de Cinétique et de Cultures Cellulaires, Service d'Hématologie, Hôtel-Dieu, Paris, France.
Abstract:
Sequential evaluation of P-glycoprotein expression was performed in 29 patients with acute nonlymphoblastic leukemia using immunocytochemistry with the C219 antibody. At diagnosis, 32% of the patients exhibited more than 5% of the P-gp(+) leukemic cells. Under chemotherapy, 62% of the patients eventually expressed a subset of P-gp positive leukemic cells. After conventional doses of cytosine-arabinoside (Ara-C) and daunorubicin or mitoxantrone, positive P-gp cells were noted in 65% of the cases. This percentage was significantly higher (p = 0.002) than the proportion of positive cases (15%) observed after regimens containing either intermediate doses of Ara-C or cyclosporine A, a P-gp modulator.
Insights
Chemotherapy can induce P-glycoprotein (P-gp) expression in acute nonlymphoblastic leukemia (ANLL) cells, potentially reducing treatment effectiveness. Strategies using P-gp modulators may improve outcomes in ANLL patients.
Area of Science:
- Oncology
- Hematology
- Molecular Biology
Background:
- P-glycoprotein (P-gp) is a transmembrane efflux pump.
- P-gp overexpression in leukemia is associated with multidrug resistance (MDR).
- Sequential evaluation of P-gp expression during treatment is crucial for understanding treatment response in acute nonlymphoblastic leukemia (ANLL).
Purpose of the Study:
- To investigate the sequential expression of P-glycoprotein (P-gp) in patients with acute nonlymphoblastic leukemia (ANLL) during chemotherapy.
- To assess the impact of different chemotherapy regimens on P-gp expression levels.
Main Methods:
- Immunocytochemistry using the C219 antibody was employed for P-gp detection.
- Sequential blood samples were collected from 29 ANLL patients.
- P-gp expression was quantified as the percentage of P-gp positive leukemic cells.
Main Results:
- At diagnosis, 32% of ANLL patients showed >5% P-gp positive leukemic cells.
- During chemotherapy, 62% of patients eventually expressed P-gp positive leukemic cells.
- Conventional doses of cytosine-arabinoside (Ara-C) and anthracyclines/mitoxantrone led to P-gp positivity in 65% of cases, significantly higher than intermediate Ara-C or cyclosporine A regimens (15%).
Conclusions:
- Chemotherapy, particularly conventional doses of Ara-C and anthracyclines/mitoxantrone, can induce P-gp expression in ANLL.
- The induction of P-gp may contribute to multidrug resistance and treatment failure.
- Regimens incorporating P-gp modulators like cyclosporine A, or intermediate-dose Ara-C, may be more effective in overcoming P-gp mediated resistance.