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T-cell receptor beta chain gene rearrangements: genetic markers of T-cell lineage and clonality

By D. M. Knowles, P. G. Pelicci and R. Dalla-Favera


We have performed a series of investigations involving T-cell receptor beta chain (T beta) gene rearrangements in benign and malignant nonhematopoietic, B-cell, and T-cell proliferations. These studies provide the conceptual basis and the operational approach for the use of T beta gene rearrangements as markers of T-cell lineage, clonality, and differentiation, analogous to immunoglobulin gene rearrangements in B cells. Southern blot hybridization analysis for T beta gene rearrangements can now be utilized to identify and distinguish between non-T cells, polyclonal T cells, and monoclonal T cells. Determination of T beta gene rearrangements will play an important role in the further investigation and classification of T-cell neoplasia. However, the identification of a genetic marker of clonality for T cells has significant diagnostic and prognostic value as well. For example, determination of the T beta gene rearrangement unique to a particular malignant T-cell clone provides a specific genetic marker for that clonal T-cell proliferation. This genetic marker of the T-cell clone may provide a useful tool for monitoring the patient's therapeutic response and clinical course for early signs of relapse. Nonetheless, our studies demonstrate that the lineage specificity of immunoglobulin and T beta gene rearrangements is not absolute. It appears that only a multiparametric approach combining extensive monoclonal antibody immunophenotypic analysis, in vitro testing for functional help and suppression, and Southern blot hybridization analysis for immunoglobulin and T beta gene rearrangements allows the conclusive and unequivocal demonstration of the B- or T-cell derivation of all lymphoid neoplasms. Lymphoid malignancies that cannot be assigned to the B- or T-cell lineage following this extensive multiparametric analysis are exceedingly uncommon

Topics: Genotype, Clone Cells, Lymphatic Diseases, Neoplasms, Humans, Recombination, Genetic, Genetic Markers, Receptors, Antigen, T-Cell, Cell Line, Settore MED/04 - Patologia Generale
Publisher: 'Elsevier BV'
Year: 1986
DOI identifier: 10.1016/S0046-8177(86)80125-3
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