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    Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia.

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    Authors
    Raghavachar, A
    Janssen, J W
    Schrezenmeier, H
    Wagner, B
    Bartram, C R
    Schulz, A S
    Hein, C
    Cowling, Graham J
    Mubarik, A
    Testa, Nydia G
    Dexter, T Michael
    Hows, J M
    Marsh, Judith C W
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    Affiliation
    Department of Medicine III, University of Ulm, Germany.
    Issue Date
    1995-10-15
    
    Metadata
    Show full item record
    Abstract
    We evaluated the methylation status of the X-linked gene phosphoglycerate kinase (PGK1) and the DXS 255 locus detected by probe M27 beta to study clonality in acquired aplastic anemia (AA). A total of 30 females were suitable for clonal analysis of peripheral blood polymorphonuclear cells (PMN) and mononuclear cells using a polymerase chain reaction-based procedure in 24 patients and Southern blotting in 9. Overall, 10 of 30 patients exhibited an imbalanced X-inactivation pattern. However, in 4 patients, analysis of constitutional DNA suggested a skewed methylation pattern and 2 further cases had to be excluded because of the lack of an appropriate control. A truly clonal pattern was thus established in 4 of 30 (13%) patients. In 7 patients who later developed clonal disorders of hematopoiesis, X-inactivation analysis did not predict this event in any case. In patients with a paroxysmal nocturnal hemoglobinuria phenotype, there was no correlation between the proportion of phosphatidylinositol glycan anchored protein (PIG-AP)-deficient blood cells and the corresponding X-inactivation pattern. X-inactivation analysis detected clonal hematopoiesis in only 3 of 10 patients with a deficiency in PIG-AP in the cell population under study, but sorting of nucleated cells on the basis of PIG-AP expression showed the clonal nature of PIG-AP-deficient cells. We conclude that the majority of patients with AA show polyclonal hematopoiesis using X-linked clonal analysis, but that minor clonal populations, such as PIG-AP-deficient cells, may not be detected unless sorted cell populations are separately analyzed.
    Citation
    Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia. 1995, 86 (8):2938-47 Blood
    Journal
    Blood
    URI
    http://hdl.handle.net/10541/97487
    PubMed ID
    7579386
    Type
    Article
    Language
    en
    ISSN
    0006-4971
    Collections
    All Paterson Institute for Cancer Research

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