Clonal hematopoiesis as defined by polymorphic X-linked loci occurs
infrequently in aplastic anemia
A Raghavachar, JW Janssen, H Schrezenmeier, B Wagner, CR Bartram, AS Schulz, C Hein, G Cowling, A Mubarik and NG Testa
Department of Medicine III, University of Ulm, Germany.
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.
Volume 86,
Issue 8,
pp. 2938-2947,
10/15/1995
Copyright © 1995 by The American Society of Hematology
