Abstract:
The author and other investigators have utilized rearrangements of immunoglobulin genes as DNA level clonal markers for neoplasms of B-cell lineage. All B-cell malignancies of mature phenotype had clonally rearranged heavy and light chain immunoglobulin genes, whereas the human T-cell neoplasms uniformly retained germline (unrearranged) light chain genes and, in most instances, germline heavy chain genes as well. In the present study, recombinant DNA technologies involving analysis of T-cell receptor gene arrangements were used to classify neoplasms that were of controversial lineage; to define the clonality of lymphoid proliferations; to assist in the diagnosis of neoplasms of the T-cell and B-cell series; and to monitor the therapy of lymphoid malignancies. Results of the study are summarized as follows: Immunoglobulin and T-cell antigen receptor genes in their germline form are separated DNA segments that are joined by recombinations during lymphocyte development. The identification of T-cell receptor gene rearrangements taken in conjunction with studies of immunoglobulin gene rearrangements aids in the elucidation of the lineage (T-cell or B-cell) and the clonality of lymphoid populations of all series. The application of this molecular genetic approach has great potential for complementing conventional marker analysis, cytogenetics, and histopathology, thus broadening the scientific basis for the classification, diagnosis, and monitoring of the therapy of lymphoid neoplasia. Interleukin-2 is a lymphokine synthesized by some T cells following activation. Resting T cells do not express interleukin-2 receptors, but receptors are rapidly expressed on T cells following the interaction of antigens, mitogens, or monoclonal antibodies with the antigen specific T-cell receptor complex. Normal resting T cells and most leukemic T-cell populations do not express interleukin-2 receptors; however, the leukemic cells of all examined patients with human T-cell lymphotropic virus I-associated adult T-cell leukemia expressed the Tac antigen. The constant display of large numbers of interleukin-2 receptors that may be aberrant may play a role in the uncontrolled growth of these leukemic cells. Patients with Tac-positive adult T-cell leukemia are being treated with anti-Tac monoclonal antibody directed toward this growth factor receptor. (37 Refs)
Keywords: Antibodies, Monoclonal/THERAPEUTIC USE Antigens, Surface/*GENETICS Base Sequence Cell Line Chromosome Aberrations DNA, Neoplasm/GENETICS DNA, Recombinant Gene Expression Regulation Human HTLV-BLV Infections/GENETICS Leukemia/*GENETICS/THERAPY Receptors, Antigen, T-Cell/GENETICS Receptors, Immunologic/*GENETICS Sezary Syndrome/GENETICS T-Lymphocytes/*IMMUNOLOGY MEETING PAPER
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