title: Association of clonal T-cell large granular lymphocyte disease and paroxysmal nocturnal haemoglobinuria (PNH): further evidence for a pathogenetic link between T cells, aplastic anaemia and PNH.
abstract: There is mounting evidence to suggest that T-cell-mediated suppression of haemopoiesis is a pathogenetic mechanism in three bone marrow failure syndromes: aplastic anaemia (AA), paroxysmal nocturnal haemoglobinuria (PNH) and myelodysplasia (MDS). T-cell microclones can be detected by sensitive polymerase chain reaction (PCR)-based methods in all three disorders. Recently, larger clonal populations of T-cell large granular lymphocytes (T-LGLs) have been observed in some patients with AA and MDS. Here, we report the development of a large clonal T-LGL population in a patient with bona fide PNH. In this patient, we defined part of the sequence of the T-cell receptor (TCR) beta-chain gene, and we have shown that the large T-LGL population emerged from a background of multiple smaller T-cell clones. Thus, T-LGL clones in AA, MDS and PNH probably expand as a result of antigenic stimulation. It is postulated that the antigen driving clonal T-cell proliferations in these disorders exists on haemopoietic stem cells.
authors.affiliation: Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Karadimitris
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Notaro
authors.forename: D J
authors.initials: DJ
authors.lastname: Araten
authors.forename: K
authors.initials: K
authors.lastname: Nafa
authors.forename: R
authors.initials: R
authors.lastname: Thertulien
authors.forename: M
authors.initials: M
authors.lastname: Ladanyi
authors.forename: A E
authors.initials: AE
authors.lastname: Stevens
authors.forename: C S
authors.initials: CS
authors.lastname: Rosenfeld
authors.forename: I A
authors.initials: IA
authors.lastname: Roberts
authors.forename: L
authors.initials: L
authors.lastname: Luzzatto
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology; D002455:Cell Division; D002999:Clone Cells; D018920:Coculture Techniques; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015458:Leukemia, T-Cell / Q000150:complications* / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000473:pathology*