Acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria: studies
on clonality [see comments]
KM Josten, JA Tooze, C Borthwick-Clarke, EC Gordon-Smith and TR Rutherford
Division of Haematology, St George's Hospital Medical School, London, UK.
We used X-chromosome methylation patterns to study clonality in aplastic
anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). AA is usually
not considered to be a clonal stem cell disorder, although this has not
been directly investigated. PNH is generally assumed to be a clonal
disorder, although there is contradictory evidence. Methylation analysis
was performed on DNA from separated granulocytes and mononuclear cells,
using the M27 beta and hypoxanthine phosphoribosyl transferase (HPRT)
probes. Six of seven AA patients showed a polyclonal pattern of X
inactivation. In contrast, five of five PNH patients showed a monoclonal
pattern. These results imply that at least 80% of the cell population
derives from a single stem cell. Because this high proportion of PNH cells
might be considered surprising, three patients were studied for membrane
expression of decay accelerating factor (DAF). In support of the DNA data,
more than 95% of the granulocytes were DAF--ve in all three cases. We
conclude that AA is predominantly a polyclonal disorder, whereas PNH is a
clonal stem cell disorder. Our data support a model in which a single PNH
stem cell has a growth advantage over other remaining stem cells and
eventually dominates hematopoiesis.
Volume 78,
Issue 12,
pp. 3162-3167,
12/15/1991
Copyright © 1991 by The American Society of Hematology
