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Multidrug Resistance in Acute Leukaemia: A Comparative Study of Immunocytochemical and RNA Slot Blot Detection of
M P Lyttelton1, S Hart1, K Ganeshaguru1
1a Department of Academic Haematology, Royal Free Hospital and School of Medicine, Pond Street, London, UK.
Abstract:
We have analysed and compared the applicability of mRNA quantitation and immunocytochemistry to the detection of the multidrug resistant gene mdr1 and its protein product P-glycoprotein (PGP) in patients with acute leukaemia. Elevated mdr1 mRNA was detected in 12 of 55 patients and PGP expression by immunocytochemistry in 10 of 27. Raised mdr1 transcript was associated with immunocytochemical positivity in 6 of 8 cases studied. 4 of 10 cases of immunocytochemical positivity were not associated with elevated mdr1 mRNA. Immunocytochemistry showed PGP expression to be heterogeneous within blast populations. In 4 cases PGP positivity was most marked in differentiated leukaemic subpopulations. PGP expression was increased in secondary acute myeloid leukaemia (AML) compared to other disease groups. No association with disease stage was detected except within the secondary leukaemias. In 40 patients studied mdr3 mRNA was raised in one patient with AML and in two remission marrows. These results indicate that further prospective studies in acute leukaemias are required using combined immunocytochemical and RNA quantitation of PGP expression.
Insights
Detecting multidrug resistance (mdr1) gene and P-glycoprotein (PGP) in acute leukaemia requires both mRNA quantitation and immunocytochemistry. PGP expression is higher in secondary acute myeloid leukaemia (AML) and can be heterogeneous within leukaemic cells.
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Multidrug resistance (MDR) is a significant challenge in acute leukaemia treatment.
- The mdr1 gene and its protein product, P-glycoprotein (PGP), are key mediators of MDR.
- Accurate detection methods for mdr1 and PGP are crucial for understanding treatment resistance.
Purpose of the Study:
- To compare the applicability of mRNA quantitation and immunocytochemistry for detecting mdr1 and PGP in acute leukaemia.
- To investigate the association between mdr1 mRNA levels and PGP expression.
- To evaluate PGP expression patterns in different acute leukaemia subtypes and disease stages.
Main Methods:
- Analysis of mdr1 mRNA levels using quantitative methods.
- Detection of PGP expression via immunocytochemistry.
- Comparison of results between the two detection methods.
- Correlation of findings with leukaemia subtypes and disease progression.
Main Results:
- Elevated mdr1 mRNA was found in 12/55 patients; PGP expression was detected in 10/27 patients.
- Raised mdr1 transcript correlated with immunocytochemical positivity in 6/8 cases.
- 4/10 cases showed PGP positivity without elevated mdr1 mRNA, indicating potential discrepancies.
- PGP expression was heterogeneous within blast populations, often marked in differentiated leukaemic subpopulations.
- PGP expression was increased in secondary acute myeloid leukaemia (AML) compared to other groups.
Conclusions:
- Both mRNA quantitation and immunocytochemistry are valuable for detecting mdr1 and PGP in acute leukaemia.
- Discrepancies between mRNA and protein detection highlight the complexity of MDR mechanisms.
- PGP expression patterns, particularly in secondary AML, warrant further investigation.
- Combined immunocytochemical and RNA quantitation approaches are recommended for future prospective studies in acute leukaemias.
