title: TCRgammadelta+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRgammadelta+ T-cells.
abstract: T-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 TCRalphabeta. Much less is known about the characteristics and pathogenesis of TCRgammadelta+ cases. We evaluated 44 patients with clonal TCRgammadelta+ T-LGL proliferations with respect to clinical data, immunophenotype and TCR gene rearrangement pattern. TCRgammadelta+ T-LGL leukemia patients had similar clinical presentations as TCRalphabeta+ 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 Vgamma9/Vdelta2 immunophenotype was found in 48% of cases and 43% of cases was positive for Vdelta1, reflecting the TCR-spectrum of normal TCRgammadelta+ T-cells in adult PB. Identification of the well-defined post-thymic Vdelta2-Jdelta1 selection determinant in all evaluable Vgamma9+/Vdelta2+ patients, is suggestive of common (super)antigen involvement in the pathogenesis of these TCRgammadelta+ T-LGL leukemia patients.
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: Sandberg
authors.forename: J
authors.initials: J
authors.lastname: Almeida
authors.forename: M
authors.initials: M
authors.lastname: Gonzalez
authors.forename: M
authors.initials: M
authors.lastname: Lima
authors.forename: P
authors.initials: P
authors.lastname: Bárcena
authors.forename: T
authors.initials: T
authors.lastname: Szczepañski
authors.forename: E J
authors.initials: EJ
authors.lastname: van Gastel-Mol
authors.forename: H
authors.initials: H
authors.lastname: Wind
authors.forename: A
authors.initials: A
authors.lastname: Balanzategui
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: J F San
authors.initials: JF
authors.lastname: Miguel
authors.forename: A
authors.initials: A
authors.lastname: Orfao
authors.forename: A W
authors.initials: AW
authors.lastname: Langerak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D007945:Leukemia, Lymphoid / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta