Definition of MRD

MRD: Minimal residual disease, evidence for the presence of residual malignant cells, even when so few cancer cells are present that they cannot be found by routine means. Tests for minimal residual disease (MRD) can detect some early tumors. In a patient who has been treated, the detection of MRD indicates that treatment is incomplete. MRD can thus distinguish who needs intensive and potentially more toxic therapy from those who do not. The general premise underlying MRD is that knowledge of MRD can effectively guide clinical care and increase cure rates.

There are a number of different techniques for detecting MRD. Among those techniques are flow cytometry and PCR (the polymerase chain reaction). These laboratory methods allow for the detection of very few abnormal cells existing among the many normal cells which may greatly outnumber them.

Flow cytometry: A flow cytometer, a laser-based instrument, is used in MRD detection to analyze a sample of cells and count any malignant cells present in the sample. The cell sample may be from blood or bone marrow. The cells are stained with a number of different antibodies specific for different antigens known to be expressed by the malignant cells. The antibodies have fluorescent tags on them to permit the flow cytometer to detect them and thereby count the malignant cells. This technology can detect one leukemic cell among 10,000 or more normal cells.

PCR: Tests for MRD using the polymerase chain reaction (PCR) can identify malignant cells based on their characteristic chromosome rearrangements. For example, PCR can detect evidence of the Philadelphia (Ph) chromosome which is found in about 95% of patients with chronic myelogenous leukemia (CML), 2%-10% of children with acute lymphoblastic leukemia (ALL), and 20%-50% of adults with ALL. The Ph arises through a reciprocal translocation between chromosomes 9 and 22 which creates a chimeric (hybrid) gene called bcr-abl that causes the malignancy. By PCR, the chimeric bcr-abl messenger RNA transcript can be detected. With PCR it is possible to detect one Ph-positive cell within a million normal cells.

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