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Detection of Clonal Immunoglobulin and T-Cell Receptor Gene Recombination in Hematological Malignancies: Monitoring Minimal Residual Disease

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A considerable number of studies on hematological malignancies have recently demonstrated that the identification of rearrangements in immunoglobulin (Ig) and T-cell receptor (TCR) genes are important tools for diagnosis and follow-up of B- and T-cell disorders. The heterogeneity of these malignancies makes it difficult to carry out a precise assessment in all patients despite well-established morphological and immunophenotyping criteria. Clonal analysis of hematological malignancies is supported by the fact that all malignant cells have a common clonal origin with identically rearranged Ig and/or TCR genes. Identification of B- or T-cell clonality in polyclonal tissue such as the blood is indicative of a lymphoproliferative process. Germline gene segments of Ig heavy chain (IGH), Ig kappa (IGK), Ig lambda (IGL) and TCR are rearranged in each lymphocyte during B- and T-cell differentiation. A specific combination of gene segments and somatic mutations occurring during this process is responsible for the wide diversity of antigen-specific receptors and antibodies. Ig and TCR rearrangements are considered the “fingerprint” of each lymphocyte and therefore can be used as tumor- specific PCR targets for detection of residual malignant cells present after treatment. Determination of minimal residual disease (MRD) has a proven prognostic value and enables effective early interventional treatment. This is becoming routinely implemented in several treatment protocols and is increasingly used in guidelines for drug therapy and stem cell transplantation. In this review we focus on: (1) the process of gene rearrangements in B- and T-cells, (2) principles of polymerase chain reaction (PCR)-based assays and real-time PCR methods commonly used to detect and follow clonal Ig and TCR rearrangements, (3) multiplex primer sets recently designed by the BIOMED-2 concerted action group, and (4) application of these techniques in MRD detection.

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Keywords: Hematological malignancy; clonal rearrangement; lymphoproliferative disease; minimal residual disease; monoclonality

Document Type: Research Article

Publication date: 2009-06-01

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  • Cardiovascular & Hematological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in cardiovascular and hematological disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cardiovascular and hematological disorders. As the discovery, identification, characterization and validation of novel human drug targets for cardiovascular and hematological drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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