What is minimal residual disease?, 53 What is PCR amplification?, 57 Molecular targets, 58
Antigen receptor gene rearrangements: immunoglobulin and TCR genes as molecular markers, 59 Quantitation of the neoplastic cells using PCR, 62 Application of PCR for residual disease detection in non-Hodgkin's lymphoma and leukemia, 64
Despite advances in the treatment of human hematological malignancies, a significant proportion of patients relapse, usually with the same malignant clone found at diagnosis. Until recently, detection of residual leukemia or lymphoma cells in marrow, blood or lymph nodes relied on light microscopy and flow cytometry. However, these techniques are not sensitive for the detection of small numbers of malignant cells. Other, more sensitive, methods are now available to assess whether early detection of residual tumor might allow intervention and prevent relapse of disease. Molecular techniques, such as the polymerase chain reaction (PCR), seem to offer highly sensitive detection of malignant DNA sequences, and this technique has been applied to a wide variety of diseases.
Many studies have now been carried out in a variety of disorders, and whilst it is true that for many hematological cancers the persistence of PCR-detectable disease predicts which patients will do less well, this does not hold true for all diseases studied. It appears that patients with some malignancies may harbor residual tumor cells for many years without ever showing any evidence of clinical relapse. This will be discussed in detail later in this chapter.
This chapter outlines the methods available, with particular emphasis on PCR amplification, and their clinical application to a variety of hematological malignancies, including lymphomas and leukemias. The molecular basis of leukemia and lymphoma is discussed in detail in Chapters 4 and 10.
Utility of molecular techniques for detection of minimal residual disease, 65
Acute leukemias, 67 Chronic leukemias, 68
Problems with PCR analysis for detection of minimal residual disease, 69 Conclusions, 70 Further reading, 70
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