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.
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.
Karadimitris
A
A
Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Li
K
K
Notaro
R
R
Araten
D J
DJ
Nafa
K
K
Thertulien
R
R
Ladanyi
M
M
Stevens
A E
AE
Rosenfeld
C S
CS
Roberts
I A
IA
Luzzatto
L
L
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*