Publication:
In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in β-thalassemia/hemoglobin E patients

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Issued Date

2005

Resource Type

Article

File Type

application/pdf

ISSN

0301472X

DOI

10.1016/j.exphem.2005.09.006

Other identifier(s)

2-s2.0-28844471024

Rights Holder(s)

Scopus

Bibliographic Citation

Experimental Hematology. Vol 33, No.12 (2005), p.1486-1492

Suggested Citation

Watanapokasin Y., Chuncharunee S., Sanmund D., Kongnium W., Winichagoon P., Rodgers G.P., Fucharoen S. In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in β-thalassemia/hemoglobin E patients. Experimental Hematology. Vol 33, No.12 (2005), p.1486-1492. doi:10.1016/j.exphem.2005.09.006 Retrieved from: https://hdl.handle.net/20.500.14740/6033

Title

In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in β-thalassemia/hemoglobin E patients

Author(s)

Watanapokasin Y.
 Chuncharunee S.
 Sanmund D.
 Kongnium W.
 Winichagoon P.
 Rodgers G.P.
 Fucharoen S.

Abstract

Objective. Some, but not all, β-thalassemia/hemoglobin E (β-thal/HbE) patients respond to hydroxyurea treatment. It would be helpful if patient responses to hydroxyurea could be screened in vitro to identify responders and nonresponders before beginning in vivo treatment. Materials and Methods. Thirteen β-Thal/HbE patients were treated with hydroxyurea orally for 2 years at a starting dose of 5 mg/kg/day for 5 days/week with escalation to a maximum of 10 mg/kg/day. For comparison, erythroid cells obtained from peripheral blood of the same patients 1 year after they had stopped hydroxyurea treatment were treated with hydroxyurea in vitro. The γ-globin mRNA was measured by real-time reverse-transcription polymerase chain reaction, fetal hemoglobin (HbF) by high-performance liquid chromatography, Gγ- and Aγ-globin chains by Triton X-100 acid urea polyacrylamide gel electrophoresis. Results. Treatment of cells in primary culture with 30 μM hydroxyurea for 96 hours significantly increased the fractional HbF content in β-Thal/HbE patients. The Gγ: Aγ-globin mRNA was induced 0.30- to 8-fold in vitro and 0.30- to 6-fold in vivo (r2 = 0.51, p = 0.16 by paired t-test); the fractional HbF content was induced 0.50- to 19-fold in vitro and 0.30- to 12-fold in vivo (r2 = 0.61, p = 0.20) and the Gγ: Aγ-globin chain ratio was increased 0.80- to 1.40-fold in vitro and 1- to 1.20-fold in vivo (r2 = 0.62, p = 0.13). Conclusion. The correlation of in vivo and in vitro results of HbF synthesis and globin mRNA suggest that in vitro testing may predict the in vivo response. © 2005 International Society for Experimental Hematology. Published by Elsevier Inc.

Subject(s)

Acid
 Gamma globin
 Hemoglobin
 Hemoglobin E
 Hemoglobin F
 Hydroxyurea
 Messenger RNA
 Triton x 100
 Urea
 Adult
 Article
 Beta thalassemia
 Clinical article
 Controlled study
 Correlation analysis
 Dose response
 Drug withdrawal
 Erythroid cell
 Female
 Hemoglobin determination
 Hemoglobin synthesis
 High performance liquid chromatography
 Human
 Human cell
 Human cell culture
 In vitro study
 In vivo study
 Male
 Peripheral circulation
 Polyacrylamide gel electrophoresis
 Priority journal
 Protein content
 Protein induction
 Protein synthesis regulation
 Quantitative analysis
 Real time polymerase chain reaction
 RNA analysis
 RNA synthesis
 Adult
 Beta-Thalassemia
 Cells, Cultured
 Drug Monitoring
 Erythroid Cells
 Female
 Fetal Hemoglobin
 Gene Expression Regulation
 Hemoglobin E
 Hemoglobinuria
 Humans
 Hydroxyurea
 Male
 Middle Aged
 Predictive Value of Tests
 Prognosis

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URI

https://hdl.handle.net/20.500.14740/6033

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Scopus: Year 1983-2021

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