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MDR1/P-GP expression as a prognostic factor in acute leukemias.
1Service d'Hématologie Biologique de l'Hôtel-Dieu, Formation de Recherche Associé Claude Bernard, Université Paris VI. Hôtel-Dieu, France.
Advances in Experimental Medicine and Biology
|September 29, 1999
Summary
P-glycoprotein (P-gp) expression in acute myelogenous leukemia (AML) correlates with treatment failure and drug resistance. Targeting P-gp may improve AML treatment outcomes.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- P-glycoprotein (P-gp) is expressed in 40-50% of acute myelogenous leukemia (AML) cells at diagnosis, increasing after treatment failure.
- MDR1 gene expression is linked to poor prognosis and drug resistance in AML patients.
Purpose of the Study:
- To investigate the prognostic value of the MDR1 phenotype in AML patients.
- To determine the correlation between P-gp expression and treatment outcomes in AML.
Main Methods:
- Analysis of large AML patient cohorts treated with anthracycline and cytosine arabinoside.
- Multivariate analysis to assess MDR1 phenotype as an independent prognostic variable.
- Correlation of in vitro drug sensitivity with P-gp expression levels.
Main Results:
- Increased MDR1 gene expression significantly correlates with treatment failure and drug resistance in AML.
- MDR1 phenotype is an independent predictor of in vivo drug resistance, comparable to karyotype and age.
- The CD34(+)/P-gp(+) phenotype is specifically linked to functional P-gp and prognostic value.
- In vitro sensitivity to anthracyclines and VP16 is strongly correlated with P-gp expression.
Conclusions:
- P-gp expression is a significant factor in AML drug resistance.
- Early intervention with P-gp modifier agents is recommended for AML treatment.
- The role of MDR1 in acute lymphoblastic leukemia (ALL) resistance is less significant compared to AML.