title: Detection of monoclonal T populations in patients with KIR-restricted chronic lymphoproliferative disorder of NK cells.
abstract: The etiology of chronic large granular lymphocyte proliferations is largely unknown. Although these disorders are characterized by the expansion of different cell types (T and natural killer) with specific genetic features and abnormalities, several lines of evidence suggest a common pathogenetic mechanism. According to this interpretation, we speculated that in patients with natural killer-type chronic lymphoproliferative disorder, together with natural killer cells, also T lymphocytes undergo a persistent antigenic pressure, possibly resulting in an ultimate clonal T-cell selection. To strengthen this hypothesis, we evaluated whether clonal T-cell populations were detectable in 48 patients with killer immunoglobulin-like receptor-restricted natural killer-type chronic lymphoproliferative disorder. At diagnosis, in half of the patients studied, we found a clearly defined clonal T-cell population, despite the fact that all cases presented with a well-characterized natural killer disorder. Follow-up analysis confirmed that the TCR gamma rearrangements were stable over the time period evaluated; furthermore, in 7 patients we demonstrated the appearance of a clonal T subset that progressively matures, leading to a switch between killer immunoglobulin-like receptor-restricted natural killer-type disorder to a monoclonal T-cell large granular lymphocytic leukemia. Our results support the hypothesis that a common mechanism is involved in the pathogenesis of these disorders.
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gattazzo
authors.affiliation: Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Teramo
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Passeri
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine.
authors.forename: Elena
authors.initials: E
authors.lastname: De March
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine.
authors.forename: Samuela
authors.initials: S
authors.lastname: Carraro
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Trimarco
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Frezzato
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine.
authors.forename: Tamara
authors.initials: T
authors.lastname: Berno
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Barilà
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Martini
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piazza
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Trentin
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute of Molecular Medicine (VIMM), Padua, Italy g.semenzato@unipd.it.
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Semenzato
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Zambello
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054066:Leukemia, Large Granular Lymphocytic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D054340:Receptors, KIR / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D011948:Receptors, Antigen, T-Cell; D054340:Receptors, KIR