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Hydroxyurea responses and fetal hemoglobin induction in β-thalassemia/HbE patients’ peripheral blood erythroid cell culture

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Abstract

Due to genetic heterogeneity of β-thalassemia (β-thal) patients, several efforts have been undertaken to determine the efficacy of hydroxyurea treatment. The aim of this work is to determine the responder and nonresponder for hydroxyurea treatment in β-thal intermedia based on γ-globin mRNA and fetal hemoglobin (HbF) induction in human erythroid progenitor cells purified from a patient’s peripheral blood. Eighteen β-thal/hemoglobin E patients [13 βE/codon41/42(-TCTT), 4 βE/codon17, and 1 βE/IVS-654], requiring blood transfusion occasionally, with Hb levels of 5.20–8.50 g/dl were studied. The relative levels of γ-globin mRNA was measured by real-time reverse-transcription polymerase chain reaction and HbF by high-performance liquid chromatography. The results indicated that erythroid progenitor cells treated with 30 μmol/l hydroxyurea for 96 h preferentially enhanced Gγ-and Aγ-globin mRNA. The mean values of Gγ-globin mRNA fold induction were higher than Aγ-globin mRNA (12±4 vs 4±0.30), the Pearson’s correlation of Gγ-and Aγ-globin mRNA was r=0.80. Induction of Gγ/Aγ globin mRNA is up to ninefold. A 30% increase in the proportion of HbF out of the total Hb was found in cultures derived from four patients, 20–30% in cultures from nine patients, and less than 20% in cultures from five patients. In cultures from only two patients, increase in the proportion of HbF was less than 3%, and Gγ/Aγ globin mRNA is less than 0.50.

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Acknowledgement

This work was supported by The Thailand Research Fund.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Sukhumvit 23, Bangkok, 10110, Thailand

    Ramida Watanapokasin

  2. Thalassemia Research Center, Institute of Science and Technology for Research and Development, Mahidol University, Nakornpathom, 73170, Thailand

    Duangmanee Sanmund, Pranee Winichagoon & Suthat Fucharoen

  3. The Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan

    Koichiro Muta

Authors
  1. Ramida Watanapokasin
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  2. Duangmanee Sanmund
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  3. Pranee Winichagoon
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  4. Koichiro Muta
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  5. Suthat Fucharoen
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Correspondence to Ramida Watanapokasin.

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Watanapokasin, R., Sanmund, D., Winichagoon, P. et al. Hydroxyurea responses and fetal hemoglobin induction in β-thalassemia/HbE patients’ peripheral blood erythroid cell culture. Ann Hematol 85, 164–169 (2006). https://doi.org/10.1007/s00277-005-0049-1

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  • DOI: https://doi.org/10.1007/s00277-005-0049-1

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