ArticleBlood2008
Neither DNA hypomethylation nor changes in the kinetics of erythroid differentiation explain 5-azacytidine's ability to induce human fetal hemoglobin.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- Epigenetic and molecular profiles of erythroid cells after hydroxyurea treatment in sickle cell anemia.Blood · 2011Trial
- Microbiota-derived metabolites in hematopoietic regulation and disease: mechanisms, context, and therapeutic perspectives.Frontiers in microbiology · 2026Review
- Modulating epigenetic modifications for cancer therapy (Review).Oncology reports · 2023Review
- Revisiting fetal hemoglobin inducers in beta-hemoglobinopathies: a review of natural products, conventional and combinatorial therapies.Molecular biology reports · 2022Review
- Exploring epigenetic and microRNA approaches for γ-globin gene regulation.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Inhibition of DNA methylation in newborns reprograms ischemia-sensitive biomarkers resulting in development of a heart ischemia-sensitive phenotype late in life.Reproductive toxicology (Elmsford, N.Y.) · 2021Article
- Molecular analysis of the erythroid phenotype of a patient with BCL11A haploinsufficiency.Blood advances · 2021Article
- Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation atScientific reports · 2021Article
- Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin.ChemMedChem · 2020Review
- The Role of Epigenetics in the Chronic Sinusitis with Nasal Polyp.Current allergy and asthma reports · 2020Review
- Proteomic Studies for the Investigation of γ-Globin Induction by Decitabine in Human Primary Erythroid Progenitor Cultures.Journal of clinical medicine · 2020Article
- Evolution of hemoglobin loci and their regulatory elements.Blood cells, molecules & diseases · 2018Review
- Epigenetic dysfunctional diseases and therapy for infection and inflammation.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- 5-azacytidine affects TET2 and histone transcription and reshapes morphology of human skin fibroblasts.Scientific reports · 2016Article
- Article
- Epigenetic regulation of fetal globin gene expression in adult erythroid cells.Translational research : the journal of laboratory and clinical medicine · 2015Review
- Article
- Natural Remedies for the Treatment of Beta-Thalassemia and Sickle Cell Anemia-Current Status and Perspectives in Fetal Hemoglobin Reactivation.International scholarly research notices · 2014Review
- β-Thalassemia due to intronic LINE-1 insertion in the β-globin gene (HBB): molecular mechanisms underlying reduced transcript levels of the β-globin(L1) allele.Human mutation · 2013Article
- Transcriptional mechanisms underlying hemoglobin synthesis.Cold Spring Harbor perspectives in medicine · 2013Review
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6 authors at 2 institutions in 1 country.
Funding
Abstract
5-azacytidine (5-Aza) is a potent inducer of fetal hemoglobin (HbF) in people with beta-thalassemia and sickle cell disease. Two models have been proposed to explain this activity. The first is based on the drug's ability to inhibit global DNA methylation, including the fetal globin genes, resulting in their activation. The second is based on 5-Aza's cytotoxicity and observations that HbF production is enhanced during marrow recovery. We tested these models using human primary cells in an in vitro erythroid differentiation system. We found that doses of 5-Aza that produce near maximal induction of gamma-globin mRNA and HbF do not alter cell growth, differentiation kinetics, or cell cycle, but do cause a localized demethylation of the gamma promoter. However, when we reduced gamma promoter methylation to levels equivalent to those seen with 5-Aza or to the lower levels seen in primary fetal erythroid cells using DNMT1 siRNA and shRNA, we observed no induction of gamma-globin mRNA or HbF. These results suggest that 5-Aza induction of HbF is not the result of global DNA demethylation or of changes in differentiation kinetics, but involves an alternative, previously unrecognized mechanism. Other results suggest that posttranscriptional regulation plays an important role in the 5-Aza response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.