Minimal residual disease (MRD) describes the lowest level of disease detectable using available methods. Previously, light microscopy, cytogenetic analysis and flow cytometry were standard techniques used for the detection of residual malignant cells in the blood and marrow of patients after treatment. However, the sensitivities of these methods do not allow identification of low levels of disease, nor do they allow accurate quantitation of malignant cell numbers. Since these residual malignant cells may be the source of ultimate relapse, there has been great interest in developing molecular techniques for the detection of residual tumor. For many years Southern blot hybridization has been the gold standard for the detection of DNA sequence alterations at specific genetic loci, but it has been largely superseded by PCR amplification of DNA sequences. Because of the power of PCR technology, we are now able to detect one residual malignant cell in a background of one million normal cells. Molecular targets for PCR-based approaches include chromosomal translocations and antigen receptor (immunoglobulin and T-cell receptor) gene rearrangements.
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