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Molecular analysis of T-cell receptor V beta chains of human T-cell chronic lymphocytic leukemia does not show intraclonal variability: implications for immunotherapy

F Picard, T Martin, F Legras, B Lioure and JL Pasquali

Laboratoire d'Immunopathologie, Hopital Central, Hopitaux Universitaires de Strasbourg, France.

Human T-cell chronic lymphocytic leukemia (T-cell CLL) is a heterogeneous disease characterized by a monoclonal malignant proliferation of T cells in which the T-cell receptors (TCRs) can be, when expressed, considered to be membrane tumor-specific antigens. Owing to the increasing number of available monoclonal antihuman TCR reagents, it could be of interest to evaluate the feasibility of anti- TCR treatment during T-cell CLL. To test the therapeutic potentiality of anti-TCR monoclonal antibodies, we first analyzed the intraclonal variability in two terminally ill patients suffering from TCR alpha beta-positive cell CLL bearing different immunophenotypes. The cDNA corresponding to the variable regions of the TCR beta chains originating from the malignant T cells were amplified, cloned into M13 phages, and sequenced. The sequence analysis of multiple independent clones showed no intraclonal variability, with no evidence for ongoing hypermutation in the V beta region genes. The relevance of these findings with regard to an anti-V beta therapy and the comparison with similar analysis during B-cell monoclonal lymphoproliferations are discussed.

Volume 82, Issue 7, pp. 2152-2156, 10/01/1993
Copyright © 1993 by The American Society of Hematology


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  Copyright © 1993 by American Society of Hematology         Online ISSN: 1528-0020