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TCRγδ+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRγδ+ T-cells

AuthorsSandberg, Y.; Almeida, Julia ; González, María; Lima, Margarida; Bárcena, Paloma; Balanzategui, Ana; San Miguel, Jesús F. ; Orfao, Alberto
Issue Date2006
PublisherNature Publishing Group
CitationLeukemia 20: 505-513 (2006)
AbstractT-cell large granular lymphocytes (LGL) proliferations range from reactive expansions of activated T cells to T-cell leukemias and show variable clinical presentation and disease course. The vast majority of T-LGL proliferations express TCRαβ. Much less is known about the characteristics and pathogenesis of TCRγδ+ cases. We evaluated 44 patients with clonal TCRγδ+ T-LGL proliferations with respect to clinical data, immunophenotype and TCR gene rearrangement pattern. TCRγδ+ T-LGL leukemia patients had similar clinical presentations as TCRγδ+ T-LGL leukemia patients. Their course was indolent and 61% of patients were symptomatic. The most common clinical manifestations were chronic cytopenias - neutropenia (48%), anemia (23%), thrombocytopenia (9%), pancytopenia (2%) - and to a lesser extent splenomegaly (18%). Also multiple associated autoimmune (34%) and hematological (14%) disorders were found. Leukemic LGLs were predominantly positive for CD2, CD5, CD7, CD8, and CD57, whereas variable expression was seen for CD16, CD56, CD11b, and CD11c. The Vγ9/Vδ2 immunophenotype was found in 48% of cases and 43% of cases was positive for Vδ1, reflecting the TCR-spectrum of normal TCRγδ+ T-cells in adult PB. Identification of the well-defined post-thymic Vδ2-Jδ1 selection determinant in all evaluable Vγ9+Nδ2+ patients, is suggestive of common (super)antigen involvement in the pathogenesis of these TCRγδ+ T-LGL leukemia patients. © 2006 Nature Publishing Group All rights reserved.
Identifiersdoi: 10.1038/sj.leu.2404112
issn: 0887-6924
e-issn: 1476-5551
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