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 Journal Article


Authors: Karadimitris, A.; Li, K.; Notaro, R.; Araten, D. J.; Nafa, K.; Thertulien, R.; Ladanyi, M.; Stevens, A. E.; Rosenfeld, C. S.; Roberts, I. A. G.; Luzzatto, L.
Article 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) β-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.
Keywords: adult; gene sequence; human cell; pathogenesis; case report; polymerase chain reaction; lymphocyte proliferation; t-lymphocytes; cell division; disease association; cyclophosphamide; t lymphocyte receptor; lymphocyte clone; hematopoietic stem cells; hematopoietic stem cell; clone cells; t lymphocyte subpopulation; paroxysmal nocturnal hemoglobinuria; aplastic anemia; hemoglobinuria, paroxysmal; coculture techniques; leukemia, t-cell; beta chain; antigenicity; anemia, aplastic; humans; human; female; priority journal; article; paroxysmal nocturnal haemoglobinuria; t-cell clones; t-cell large granular lymphocyte disease; gene rearrangement, beta-chain t-cell antigen receptor
Journal Title: British Journal of Haematology
Volume: 115
Issue: 4
ISSN: 0007-1048
Publisher: John Wiley & Sons  
Date Published: 2001-12-01
Start Page: 1010
End Page: 1014
Language: English
DOI: 10.1046/j.1365-2141.2001.03172.x
PUBMED: 11843843
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Ke Li
    2 Li
  2. Khedoudja Nafa
    184 Nafa
  3. Rosario Notaro
    22 Notaro
  4. Marc Ladanyi
    870 Ladanyi
  5. David Araten
    20 Araten
  6. Lucio Luzzatto
    104 Luzzatto