Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia.
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
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
Citations
Altmetric:
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.
Description
Date
1995-10-15
Publisher
Collections
Keywords
Aplastic Anaemia
Haematopoiesis
Haematopoiesis
Type
Article
Citation
Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia. 1995, 86 (8):2938-47 Blood