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  • Title: T-large granular lymphocyte leukemia: current molecular concepts.
    Author: Wlodarski MW, Schade AE, Maciejewski JP.
    Journal: Hematology; 2006 Aug; 11(4):245-56. PubMed ID: 17178663.
    Abstract:
    T-large granular lymphocyte (T-LGL) leukemia is a chronic and often indolent T cell lymphoproliferation characterized by extreme expansion of a semi-autonomous cytotoxic T lymphocyte (CTL) clone. Clinically, T-LGL can be associated with various cytopenias; neutropenia constitutes the most frequent manifestation. LGL clone represents a pathologic counterpart of the cytotoxic effector T cell but an abnormal memory CD8 cell seems to provide the supply of the matured LGL population. Analysis of clonal T cell receptor (TCR) rearrangement and complementarity determining region 3 (CDR3) of the TCR beta-chain is a useful tool to investigate clonal expansions, track the frequency of expanded clones and also clinically useful to monitor the response to therapy. The lessons learned from molecular analysis of clonal repertoire support a clinically-derived conclusion that the LGL clone arises in the context of an initially polyclonal immune response or an autoimmune process. Consequently, specific manifestations of T-LGL may be a result of the recognition spectrum of the transformed clone and the cytokines it produces. Due to the often monoclonal manifestation, T-LGL constitutes a suitable model to investigate polyclonal CTL-mediated processes. Application of new technologies, including TCR repertoire analysis by sequencing, clonotypic quantitative PCR and VB flow cytometry facilitate clinical diagnosis and may allow insights into the regulation of TCR repertoire and consequences resulting from the contraction of clonal diversity.
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