ArticleBlood2005
The hydroxyurea-induced small GTP-binding protein SAR modulates gamma-globin gene expression in human erythroid cells.
Article in Blood, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease.Expert review of hematology · 2015Pooled it
- Population pharmacokinetics and pharmacodynamics of hydroxyurea in sickle cell anemia patients, a basis for optimizing the dosing regimen.Orphanet journal of rare diseases · 2011Trial
- Differential MicroRNA Profiles Associated With the Hydroxyurea-InducibleJournal of hematology · 2025Article
- SAR1A Induces Cell Growth and Epithelial-Mesenchymal Transition Through the PI3K/AKT/mTOR Pathway in Head and Neck Squamous Cell Carcinoma: An In Vitro and In Vivo Study.Biomedicines · 2024Article
- Single nucleotide polymorphisms inEJHaem · 2022Article
- Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Mathematical Modeling of Hydroxyurea Therapy in Individuals with Sickle Cell Disease.Pharmaceutics · 2022Article
- Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells.International journal of molecular sciences · 2021Article
- Do Genetic Polymorphisms Affect Fetal Hemoglobin (HbF) Levels in Patients With Sickle Cell Anemia Treated With Hydroxyurea? A Systematic Review and Pathway Analysis.Frontiers in pharmacology · 2021Review
- Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism.The pharmacogenomics journal · 2018Review
- Epigenetic silencing of TMEM176A activates ERK signaling in human hepatocellular carcinoma.Clinical epigenetics · 2018Article
- SAR1a promoter polymorphisms are not associated with fetal hemoglobin in patients with sickle cell disease from Cameroon.BMC research notes · 2017Article
- Sustained enhancement of OCTN1 transporter expression in association with hydroxyurea induced γ-globin expression in erythroid progenitors.Experimental hematology · 2017Article
- Article
- Hydroxyurea down-regulates BCL11A, KLF-1 and MYB through miRNA-mediated actions to induce γ-globin expression: implications for new therapeutic approaches of sickle cell disease.Clinical and translational medicine · 2016Article
- Cell signaling pathways involved in drug-mediated fetal hemoglobin induction: Strategies to treat sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2015Review
- A step forward back to (induced) fetal.Blood · 2014Article
- Hydroxyurea-inducible SAR1 gene acts through the Giα/JNK/Jun pathway to regulate γ-globin expression.Blood · 2014Article
- Emerging science of hydroxyurea therapy for pediatric sickle cell disease.Pediatric research · 2014Review
- Evaluation of Signaling Pathways Involved in γ-Globin Gene Induction Using Fetal Hemoglobin Inducer Drugs.International journal of hematology-oncology and stem cell research · 2013Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hydroxyurea (HU), a drug effective in the treatment of sickle cell disease, is thought to indirectly promote fetal hemoglobin (Hb F) production by perturbing the maturation of erythroid precursors. The molecular mechanisms involved in HU-mediated regulation of gamma-globin expression are currently unclear. We identified an HU-induced small guanosine triphosphate (GTP)-binding protein, secretion-associated and RAS-related (SAR) protein, in adult erythroid cells using differential display. Stable SAR expression in K562 cells increased gamma-globin mRNA expression and resulted in macrocytosis. The cells appeared immature. SAR-mediated induction of gamma-globin also inhibited K562 cell growth by causing arrest in G1/S, apoptosis, and delay of maturation, cellular changes consistent with the previously known effects of HU on erythroid cells. SAR also enhanced both gamma- and beta-globin transcription in primary bone marrow CD34+ cells, with a greater effect on gamma-globin than on beta-globin. Although up-regulation of GATA-2 and p21 was observed both in SAR-expressing cells and HU-treated K562 cells, phosphatidylinositol 3 (PI3) kinase and phosphorylated ERK were inhibited specifically in SAR-expressing cells. These data reveal a novel role of SAR distinct from its previously known protein-trafficking function. We suggest that SAR may participate in both erythroid cell growth and gamma-globin production by regulating PI3 kinase/extracellular protein-related kinase (ERK) and GATA-2/p21-dependent signal transduction pathways.
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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.