Please use this identifier to cite or link to this item: http://ir.swu.ac.th/jspui/handle/123456789/15069
Title: In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in β-thalassemia/hemoglobin E patients
Authors: Watanapokasin Y.
Chuncharunee S.
Sanmund D.
Kongnium W.
Winichagoon P.
Rodgers G.P.
Fucharoen S.
Keywords: 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
Issue Date: 2005
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.
URI: https://www.scopus.com/inward/record.uri?eid=2-s2.0-28844471024&doi=10.1016%2fj.exphem.2005.09.006&partnerID=40&md5=dec308ff9b56a09b756a4c32cc18b526
http://ir.swu.ac.th/jspui/handle/123456789/15069
ISSN: 0301472X
Appears in Collections:Scopus 1983-2021

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