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On the induction of fetal hemoglobin by butyrates: in vivo and in vitro
studies with sodium butyrate and comparison of combination treatments with
5-AzaC and AraC
P Constantoulakis, G Knitter and G Stamatoyannopoulos
Department of Medicine, University of Washington, Seattle 98195.
To obtain information on the cellular mechanism of induction of fetal
hemoglobin (HbF) by sodium butyrate (NaB), we treated adult baboons with
NaB and assessed its effects on HbF expression. Infusion of NaB increased F
reticulocytes and F-positive CFUe and e-cluster colonies without induction
of reticulocytosis or increase in progenitor cell numbers. Addition of NaB
in bone marrow cultures increased the frequency of F-positive CFUe and
e-clusters without increasing progenitor cell numbers. NaB induced HbF in
human adult BFUe cultures and increased the gamma/gamma + beta globin chain
and mRNA ratios in short-term incubations of culture-derived erythroblasts.
There was a synergistic induction of HbF by NaB and 5-azacytidine (5-azaC),
but not when the animal was treated with NaB and cytarabine (AraC). Our
results suggest that the activation of gamma-globin expression by NaB
reflects an action of this compound on globin genes or globin chromatin.
Volume 74,
Issue 6,
pp. 1963-1971,
11/01/1989
Copyright © 1989 by The American Society of Hematology
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