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Multidrug resistance-associated protein in acute myeloid leukemia: No impact on treatment outcome
M Filipits1, R W Suchomel, S Zöchbauer
1Divisions of Oncology and Hematology, Department of Internal Medicine I, University of Vienna Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Abstract:
Drug resistance remains a major problem in the treatment of patients with acute myeloid leukemia (AML). Expression of the MDR1 gene in leukemic cells was shown previously to be associated with worse clinical outcome of the patients. The multidrug resistance-associated protein (MRP) has been shown recently to be another protein causing the multidrug resistance phenotype in cell lines, but its impact on clinical outcome in patients with AML remains to be proven. To determine the clinical significance of MRP in patients with de novo AML, we have studied the MRP expression in leukemic cells and its association with both response to induction chemotherapy and survival of the patients. MRP gene expression was determined by immuno-cytochemistry (n = 80) by means of the monoclonal antibodies QCRL-1 and QCRL-3. MRP expression was low, intermediate, and high in 19, 55, and 26% of the patients, respectively. High MRP expression was independent of age and sex of the patients, WBC count, and percentage of blasts. However, high MRP expression was more frequent in the FAB M5 subtype as compared to the other subtypes. MRP expression had no impact on clinical outcome. The complete remission rates were 65, 68, and 63% for patients with low, intermediate, and high expression, respectively. Overall survival was also independent of MRP expression. In contrast, patients with P-glycoprotein-positive AML had lower complete remission rates and shorter durations of survival. These data indicate that MRP is expressed in patients with de novo AML but, in contrast to P-glycoprotein, does not predict for outcome of induction chemotherapy or survival.
Insights
Multidrug resistance-associated protein (MRP) is present in acute myeloid leukemia (AML) cells but does not predict treatment outcomes. Unlike P-glycoprotein, MRP expression does not impact chemotherapy response or patient survival in de novo AML.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Drug resistance is a significant challenge in acute myeloid leukemia (AML) treatment.
- The MDR1 gene and P-glycoprotein are known contributors to multidrug resistance in AML.
- The role of multidrug resistance-associated protein (MRP) in AML clinical outcomes requires further investigation.
Purpose of the Study:
- To investigate the clinical significance of MRP expression in de novo AML patients.
- To determine the association between MRP expression and response to induction chemotherapy.
- To assess the impact of MRP expression on patient survival.
Main Methods:
- Immuno-cytochemistry was used to determine MRP expression in leukemic cells from 80 de novo AML patients.
- Monoclonal antibodies QCRL-1 and QCRL-3 were employed for MRP detection.
- Statistical analysis correlated MRP expression levels with complete remission rates and overall survival.
Main Results:
- MRP expression was detected in all de novo AML patients, with varying levels (low, intermediate, high).
- High MRP expression was not associated with patient demographics, WBC count, or blast percentage.
- High MRP expression was more prevalent in the FAB M5 subtype.
- MRP expression did not significantly impact complete remission rates or overall survival.
- In contrast, P-glycoprotein-positive AML patients showed poorer outcomes.
Conclusions:
- MRP is expressed in de novo AML, but its levels do not serve as a predictive marker for chemotherapy response or survival.
- P-glycoprotein remains a significant prognostic factor in AML, unlike MRP.
- Further research may explore combined markers or alternative therapeutic strategies for drug-resistant AML.