Document Detail


Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine.
MedLine Citation:
PMID:  6197114     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In vivo observations on the kinetics of F cells and of fetal hemoglobin (HbF) synthesis and in vitro studies of erythroid progenitors, their number, and the gamma-gene expression in their progeny were carried out in baboons (Papio cynocephalus) treated with 5-azacytidine. Maximum effect on the increase of HbF production in vivo was observed only when an expanded erythroid marrow population was present. In these animals, as well as in normal animals, treatment resulted in a significant reduction of the late erythroid progenitor cell pools (erythroid clusters and erythroid colony-forming units, CFU-E) in the marrow. This reduction was more pronounced among those progenitors grown in the absence of added erythropoietin, and it was followed by a rebound a few days after treatment cessation, reflecting the accumulation of regenerating progenitors. An early increase in the in vitro synthesis of HbF in erythroid clusters and CFU-E colonies was observed. This increase was further documented at the cellular level, with immunofluorescent labeling of colonies with monoclonal anti-gamma-globin chain antibodies. In contrast to the findings in late progenitors, the number of erythroid burst-forming unit (BFU-E) colonies and the synthesis of HbF in these colonies was not influenced significantly by 5-azacytidine treatment. It is proposed that the toxic effects of 5-azacytidine on late progenitors, leading to faster mobilization of earlier progenitors to the next more mature compartment, play a role in the in vivo augmentation of HbF synthesis by this drug. This perturbation in the progenitor cell population kinetics and the presumed hypomethylation of the surviving differentiating cells may act synergistically to produce a maximum HbF response after 5-azacytidine treatment.
Authors:
A T Torrealba-de Ron; T Papayannopoulou; M S Knapp; M F Fu; G Knitter; G Stamatoyannopoulos
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Blood     Volume:  63     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1984 Jan 
Date Detail:
Created Date:  1984-02-14     Completed Date:  1984-02-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  201-10     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Anemia / blood,  etiology
Animals
Azacitidine / administration & dosage*
Bloodletting
Bone Marrow Cells
Cell Count
Colony-Forming Units Assay
Erythrocytes / cytology*,  drug effects,  immunology
Erythropoiesis / drug effects*
Fetal Hemoglobin / biosynthesis*,  immunology
Fluorescent Antibody Technique
Globins / biosynthesis
Hematopoietic Stem Cells / cytology*,  drug effects
Hemoglobin A / immunology
Male
Papio
Reticulocytes
Grant Support
ID/Acronym/Agency:
HL 20899/HL/NHLBI NIH HHS; RR 00166/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
320-67-2/Azacitidine; 9004-22-2/Globins; 9034-51-9/Hemoglobin A; 9034-63-3/Fetal Hemoglobin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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