Document Detail


Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex.
MedLine Citation:
PMID:  6192443     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increased production of fetal hemoglobin (HbF) was observed in a patient with sickle cell anemia treated with 5-azacytidine. Each of four courses of therapy resulted in a rapid and prolonged increase in the percentage of HbF containing reticulocytes (F reticulocytes) and HbF containing erythrocytes (F cells). The percentage of HbF in peripheral blood rose from 1.8 to 8.9%. The rise in HbF production was accompanied by an increase in peripheral blood hemoglobin concentration from 8 to 12 g/dl and an increase in mean erythrocyte volume. Treatment with 5-azacytidine resulted in hypomethylation of total genomic and a Y-chromosome-specific DNA fragment isolated from both peripheral blood and bone marrow. Of 15 restriction enzyme sites around the gamma-delta-beta-globin gene complex, only 2 became hypomethylated: one 107 bases 5' to the gamma G and the other 107 bases 5' to the gamma A globin genes.
Authors:
S Charache; G Dover; K Smith; C C Talbot; M Moyer; S Boyer
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  80     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1983 Aug 
Date Detail:
Created Date:  1983-09-09     Completed Date:  1983-09-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4842-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Anemia, Sickle Cell / drug therapy*,  genetics
Azacitidine / therapeutic use*
DNA / genetics*,  isolation & purification
DNA Restriction Enzymes
Fetal Hemoglobin / genetics*
Genes / drug effects*
Globins / genetics*
Humans
Male
Methylation
Nucleic Acid Hybridization
Grant Support
ID/Acronym/Agency:
HL027996/HL/NHLBI NIH HHS; HL15026/HL/NHLBI NIH HHS; HL28028/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
320-67-2/Azacitidine; 9004-22-2/Globins; 9007-49-2/DNA; 9034-63-3/Fetal Hemoglobin; EC 3.1.21.-/DNA Restriction Enzymes
Comments/Corrections

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