Document Detail


Selectively increased growth of fetal hemoglobin-expressing adult erythroid progenitors after brief treatment of early progenitors with transforming growth factor beta.
MedLine Citation:
PMID:  10779447     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have studied the effect of transforming growth factor beta (TGFbeta) on erythropoiesis in cultures from adult peripheral blood, using flow cytometric enumeration of fetal hemoglobin (HbF)-containing cells. TGFbeta caused a dramatic increase in the proportions of cells that accumulated HbF together with adult hemoglobin (HbA) (F+A+ cells). This highly significant (P <.0001) increase in F+ cell proportion was achieved by TGFbeta treatment during the first 4 days of culture and was sustained during further culture expansion in the absence of TGFbeta. The increase in F+ cell proportions did not depend on the cytokine combination (EPO+SCF+IL3, EPO+SCF, EPO+IL3, SCF+IL3) used during the phase of TGFbeta treatment. Increased F+ cell proportions were paralleled by an increased molecular ratio of HbF/ HbF+ HbA, measured by cation exchange high-performance liquid chromatography (HPLC). In addition to the effect on F+ cell proportions, TGFbeta caused a dramatic increase in overall cell division potential. By the time cultures reached terminal growth arrest (12-14 days in controls and 18-26 days after TGFbeta), the overall numbers of F+ cells produced per initially seeded clonogenic cell was approximately 10 times higher in the TGFbeta-treated cultures than in the controls. We propose to investigate whether the TGFbeta-induced increase in relative and absolute numbers of nucleated F+ cells, as demonstrated in vitro, can be translated into increased F+ erythrocytes in vivo, allowing therapeutic application for some beta-hemoglobinopathies. (Blood. 2000;95:2967-2974)
Authors:
R M Bohmer; T A Campbell; D W Bianchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood     Volume:  95     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-05-23     Completed Date:  2000-05-23     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2967-74     Citation Subset:  AIM; IM    
Affiliation:
Division of Genetics, Department of Pediatrics, New England Medical Center and Tufts University Medical School, Boston, MA 02111, USA. ralph.bohmer@es.nemc.org
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MeSH Terms
Descriptor/Qualifier:
Adult
Cell Division / drug effects
Cells, Cultured
Erythroid Precursor Cells / cytology*,  drug effects,  metabolism*
Fetal Hemoglobin / metabolism*
Hemoglobin A / metabolism*
Humans
Kinetics
Time Factors
Transforming Growth Factor beta / pharmacology*
Chemical
Reg. No./Substance:
0/Transforming Growth Factor beta; 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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