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Erythroblastic inclusions in dominantly inherited beta thalassemias
PJ Ho, SN Wickramasinghe, DC Rees, MJ Lee, A Eden and SL Thein
Medical Research Council Molecular Haematology Unit, John Radcliffe
Hospital, Headington, Oxford, UK.
While the precipitation of unstable variant beta-globin chains has been
implicated as a major pathogenic mechanism in dominantly inherited beta
thalassemia, their instability and presence in intra-erythroblastic
inclusions have not been conclusively shown. We report the investigation of
two cases of dominantly inherited beta thalassemia due to heterozygosity
for the beta-codon 121 G-T mutation. In one case, we were able to
demonstrate the presence of an abnormal beta-globin chain in both
peripheral blood reticulocytes and bone marrow erythroblasts, and to assess
its stability in relation to the substantial amounts of mutant beta mRNA
transcript. The serum transferrin receptor (TfR) level was markedly
increased, an indication of increased erythropoietic activity. In both
cases, we could show by immunoelectron microscopy that the
intra-erythroblastic inclusion bodies, a prominent feature of diseases in
this category, contained not only precipitated alpha-globin chains, but
also beta chains. The data confirm previous suggestions that the cellular
pathology underlying this group of beta thalassemias is related to the
synthesis of highly unstable beta-globin chain variants, which fail to form
functional tetramers and precipitate intracellularly with the concomitant
excess alpha chains, leading to increased ineffective erythropoiesis.
Volume 89,
Issue 1,
pp. 322-328,
01/01/1997
Copyright © 1997 by The American Society of Hematology
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