Detection of minimal residual disease in acute leukemia patients
J J van Dongen1, T Szczepański, M A de Bruijn
1Department of Immunology, Erasmus University Rotterdam, The Netherlands.
Abstract:
Diagnostic techniques, routinely used in clinical practice for monitoring acute leukemia patients, are able to detect only 1-5% of malignant cells. At present, two main techniques are being introduced for detection of minimal residual disease (MRD) in leukemia, namely immunological marker analysis and the polymerase chain reaction (PCR) technique with general sensitivity of 10(-4)-10(-5). Immunological marker analysis allows detection of unusual and aberrant immunophenotypes, and is usually performed by flow cytometry. PCR analysis allows detection of leukemia-specific DNA sequences, such as fusion regions of chromosome aberrations and junctional regions of rearranged immunoglogulin (Ig) genes and T-cell receptor (TcR) genes. The applicability of the immunophenotyping and PCR-mediated MRD techniques is dependent on the type of leukemia. In virtually all acute lymphoblastic leukemias, PCR analysis of Ig and TcR genes can be used, and immunophenotypic MRD detection is also possible in 70-80% of cases. In AML, immunophenotypic MRD detection can be applied in approximately 80% of cases and PCR analysis of chromosome aberrations in 25-40%. Each MRD technique has its advantages and limitations, which have to be weighed carefully to make an appropriate choice. Furthermore, standardization of the MRD techniques is needed before they are used for stratification or adaptation of treatment protocols. Finally, the clinical impact of MRD detection for the various subtypes of acute leukemias has to be established.
Insights
Detecting minimal residual disease (MRD) in leukemia requires advanced techniques beyond standard diagnostics. Immunological marker analysis and polymerase chain reaction (PCR) offer greater sensitivity for monitoring leukemia patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Standard diagnostic methods for acute leukemia detect only 1-5% of malignant cells.
- Minimal residual disease (MRD) monitoring is crucial for leukemia patient management.
- Current research focuses on highly sensitive techniques for MRD detection.
Purpose of the Study:
- To compare the applicability and sensitivity of immunological marker analysis and polymerase chain reaction (PCR) for minimal residual disease (MRD) detection in acute leukemia.
- To evaluate the strengths and limitations of different MRD detection techniques across various leukemia subtypes.
- To highlight the need for standardization and further clinical validation of MRD detection methods.
Main Methods:
- Immunological marker analysis, primarily using flow cytometry, to detect aberrant immunophenotypes.
- Polymerase chain reaction (PCR) analysis to detect leukemia-specific DNA sequences, including fusion genes and rearranged immunoglobulin (Ig) and T-cell receptor (TcR) genes.
- Assessment of technique applicability based on acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) subtypes.
Main Results:
- PCR offers high sensitivity (10(-4)-10(-5)) for MRD detection in leukemia.
- Immunophenotypic analysis is applicable in 70-80% of ALL cases and 80% of AML cases.
- PCR analysis of chromosome aberrations is applicable in 25-40% of AML cases.
Conclusions:
- Both immunophenotyping and PCR are valuable for MRD detection, with applicability varying by leukemia type.
- Standardization of MRD techniques is essential for treatment stratification and adaptation.
- Further research is needed to establish the clinical impact of MRD detection across different acute leukemia subtypes.
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