Cited by 102Hemoglobinopathies and Related DisordersHemoglobin structure and functionHematopoietic Stem Cell Transplantation

Hydroxyurea increases fetal hemoglobin in cultured erythroid cells derived from normal individuals and patients with sickle cell anemia or beta-thalassemia

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Fibach, E, Burke, LP, Schechter, AN, Noguchi, CT, Rodgers, GP·1993·Blood

Abstract

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.

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Crossref · 10.1182/blood.v81.6.1630.1630

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  • Exposure of developing human erythroid cells to in vitro culture conditions variably elevates basal fetal globin gene expression.

    “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

  • The human γ-globin genes are in a poised and therefore more responsive state when compared to the murine embryonic genes.

    “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

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Research works printed but not linked: 3

  1. 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
  2. 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
  3. 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

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Authors
Fibach, E., Burke, L., Schechter, A., Noguchi, C., & Rodgers, G.
Affiliations
  • Hadassah Medical Center (IL)
  • Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Venue
Blood
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
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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

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