Acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria: studies on clonality

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, alth...

Full description

Saved in:
Bibliographic Details
Published in:Blood 1991-12, Vol.78 (12), p.3162-3167
Main Authors: Josten, K M, Tooze, J A, Borthwick-Clarke, C, Gordon-Smith, E C, Rutherford, T R
Format: Article
Language:English
Subjects:
Adult
Aged
Anemia, Aplastic - pathology
Blotting, Southern
CD55 Antigens
Clone Cells - pathology
Complement Inactivator Proteins - analysis
DNA - analysis
Female
Granulocytes - pathology
Hematopoietic Stem Cells - pathology
Hemoglobinuria, Paroxysmal - pathology
Humans
Lymphocytes - pathology
Membrane Proteins - analysis
Middle Aged
Polymorphism, Genetic
Repetitive Sequences, Nucleic Acid
X Chromosome
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V78.12.3162.3162