AJP - Cell Physiology, Vol 261, Issue 3 C448-C454, Copyright © 1991 by American Physiological Society
Disappearance of the protein of a somatic mutation: a possible example of stem cell inactivation
J. G. Adams, C. L. Hardy and M. H. Steinberg
Department of Medicine, University of Mississippi School of Medicine, Jackson.
The low concentration of the hemoglobin variant, Hb Vicksburg
(leucine-beta-75 deleted), and a profound deficit of its mRNA led us to
postulate that a beta(+)-thalassemia mutation existed in cis to the coding
region mutation, suppressing its synthesis. We examined blood from this
patient 6, 8, and 10 yr after our initial studies, using methods of
analysis unavailable initially. We found 1) mutations causing beta(+)-(-88
C----T) and beta 0-(849 A----G) thalassemia; 2) that the proportion of Hb
Vicksburg in erythrocytes fell over time, from 8 to 4%, and ultimately
disappeared; and 3) that the mutation causing Hb Vicksburg was not
detectable in genomic DNA isolated from blood leukocytes when this variant
was present in hemolysate. We postulate that Hb Vicksburg arose from a
somatic mutation of a beta(+)-thalassemia gene in an erythroid-committed
stem cell. Its gradual disappearance suggests the cycling of stem cells,
with inactivation of different clones over time.
