The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Hydroxyurea increases fetal hemoglobin in cultured erythroid cells derived from normal individuals and patients with sickle cell anemia or beta-thalassemia
Open accessAbstract
Hydroxyurea (HU), an inhibitor of DNA synthesis, has been shown to increase fetal hemoglobin (HbF) levels in patients with sickle cell anemia and in some patients with beta-thalassemia. However, until now there have not been good in vitro model systems that simulate this effect for study of the molecular and cellular mechanism(s) involved in perturbing the normal ontogeny of the globin genes. We analyzed the cellular effects of HU using a two-phase liquid culture procedure (Fibach et al: Blood 73:100, 1989) in which human peripheral blood-derived progenitor cells undergo proliferation and differentiation. HU was found to have multiple effects on these cultured cells: (1) an increase in the proportion of HbF produced; (2) a decrease in cell number due to inhibition of cell proliferation; (3) an increase in hemoglobin content per cell (mean corpuscular hemoglobin [MCH]); and (4) an increase in cell size (mean corpuscular volume). The extent of these effects was related to the HU dose and time of addition. When added to cell cultures from normal individuals, 4 days following their exposure to erythropoietin (EPO), 100 mumol/L HU caused a 1.3- to 3.5-fold increase in the proportion of HbF, from 0.4% to 5.2% (mean 1.6) in untreated to 1.5% to 8.2% (mean 3.1) in HU-treated cultures and a 45% +/- 10% increase in MCH but only a 25% +/- 7% decrease in cell number on day 13. Cultures of cells derived from five patients with sickle cell anemia have shown a twofold to fivefold increase in the percentage of Hb F following addition of HU while four patients with beta-thalassemia showed a 1.3- to 6.2-fold increase. We believe that this primary cell culture procedure should prove useful in studying the cellular and molecular mechanisms of pharmacologic induction of HbF and might provide a valuable predictive assay system for evaluation of the response of individual patients with hemoglobinopathies to HU and similar agents.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Exposure of developing human erythroid cells to in vitro culture conditions variably elevates basal fetal globin gene expression, suggesting that the human γ-globin genes are in a poised and therefore more responsive state when compared to the murine embryonic genes. (Fibach et al., 1993).”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Fibach et al., 1993
In the citing paper
“Exposure of developing human erythroid cells to in vitro culture conditions variably elevates basal fetal globin gene expression, suggesting that the human γ-globin genes are in a poised and therefore more responsive state when compared to the murine embryonic genes. (Fibach et al., 1993).”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Fibach et al., 1993
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome
Lozzio, C., & Lozzio, B. (1975) · Blood · doi:10.1182/blood.v45.3.321.bloodjournal453321 · Cited by 2,978
Friend, C., Scher, W., Holland, J. G., & Satô, T. (1971) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.68.2.378 · Cited by 1,352
5-Azacytidine Selectively Increases γ-Globin Synthesis in a Patient with β+Thalassemia
Ley, T. J., DeSimone, J., Anagnou, N. P., Keller, G. H., Humphries, R. K., Turner, P. H., Young, N. S., Heller, P., & Nienhuis, A. W. (1982) · New England Journal of Medicine · doi:10.1056/nejm198212093072401 · Cited by 490
Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia [see comments]
Charache, S., Dover, G. J., Moore, R. D., Eckert, S. V., Ballas, S., Koshy, M., Milner, P., Orringer, E., Phillips, G., & Platt, O. (1992) · Blood · doi:10.1182/blood.v79.10.2555.2555 · Cited by 438
Differentiation in erythroleukemic cells and their somatic hybrids.
Orkin, S. H., Hárosi, F. I., & Leder, P. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.1.98 · Cited by 426
5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons.
DeSimone, J., Heller, P., Hall, L., & Zwiers, D. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.14.4428 · Cited by 384
Hematologic Responses of Patients with Sickle Cell Disease to Treatment with Hydroxyurea
Rodgers, G. P., Dover, G. J., Noguchi, C. T., Schechter, A. N., & Nienhuis, A. W. (1990) · New England Journal of Medicine · doi:10.1056/nejm199004123221504 · Cited by 277
Self-citationProliferation and maturation of human erythroid progenitors in liquid culture
Fibach, E., Manor, D., Oppenheim, A., & Rachmilewitz, E. A. (1989) · Blood · doi:10.1182/blood.v73.1.100.100 · Cited by 272
Self-citationCharache, S., Dover, G., Smith, K. D., Talbot, C. C., Moyer, M. A., & Boyer, S. H. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.15.4842 · Cited by 270
Ley, T. J., DeSimone, J., Noguchi, C., Turner, P., Schechter, A. N., Heller, P., & Nienhuis, A. (1983) · Blood · doi:10.1182/blood.v62.2.370.370 · Cited by 249
Self-citation
Research works printed but not linked: 3
- Bunn HF, Forget B F Hemoglobins: Molecular, Genetic and Clinical Aspects. Philadelphia, PA, Saunders, I986 3. Weatherall DJ, Clegg JB: The Thalassemia Syndromes (ed 3). Oxford, UK, Blackwell Scientific, 198 1
- Schechter AN, Noguchi CT, Rodgers GP: Sickle cell anemia, in Stamatoyannaopoulos G, Nienhuis AW, Leder P, Majerus PW (eds): Molecular Basis of Blood Diseases. Philadelphia, PA, Saunders, 1987, p 179
- Bessin M, Lessis LS, Beutler E: Morphology of the erythron, in Williams WJ, Beutler E, Erslev AJ, Lichtman MA (eds): Hema- tology. New York, NY, McGraw-Hill, 1990, p 257
Cited by
Sorted by citations
Items 101–102 of 102
Déterminants de la réponse à l'Hydroxyurée au cours du traitement de la drépanocytose
Rakotoson, M. G. (2016) · theses.fr (ABES) · doi:10.70675/29250363zfe0bz41aaz860azcc473ae41b1f
Hui, M., Xu, Z., Li, Q., Zhan, Y., Shi, Y., Wu, F., Lu, L., Zhang, M., Yang, H., Yu, S., et al. (2026) · International Journal of Dentistry · doi:10.1155/ijod/3607127
Metadata
- Authors
- Fibach, E., Burke, L., Schechter, A., Noguchi, C., & Rodgers, G.
- Affiliations
- Hadassah Medical Center (IL)
- Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
- ORCID
- Fibach, E
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1993-03-15
- Volume
- 81
- Issue
- 6
- Pages
- 1630-1635
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W324137543
- Cited by
- 102
- References
- 28
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 5 · 2012: 1
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- hydroxyurea, fetal hemoglobin, sickle cell disease, beta-thalassemia, erythroid progenitor cells, erythropoiesis, globin gene regulation, erythropoietin, cell proliferation inhibition, hemoglobin levels, predictive assays, hemoglobinopathies
- MeSH terms
- Anemia, Sickle Cell, Cells, Cultured, Fetal Hemoglobin, Humans, Hydroxyurea, Erythroid Precursor Cells, beta-Thalassemia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
