| 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 |
Related Documents
:
|
2649184 - Limits of phenotypic markers for the diagnosis of megakaryoblastic leukemia. 3428504 - Immunohistochemical analysis of the distribution of histone h5 and hemoglobin during ch... 10977944 - Ability of peritoneal exudate cells to trigger various mechanisms of erythroid differen... 11112384 - Erythropoietin-dependent suppression of the expression of the beta subunits of the inte... 12616484 - Recognition of hla-g by the nk cell receptor kir2dl4 is not essential for human reprodu... 2476284 - A simple method for estrogen receptor antigen preservation in cytologic specimens conta... |
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 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Free energy potential for aggregation of erythrocytes and phosphatidylcholine/phosphatidylserine ves...
Next Document: Increased HbF in sickle cell anemia is determined by a factor linked to the beta S gene from one par...