Abbas Najjari1, Mohsen Asouri2, Ladan Hosseini Gouhari3, Haleh Akhavan Niaki4, Amir Sasan Mozaffari Nejad5, Seyyedeh Masoumeh Eslami6, Hassan Abolghasemi7, Ramin Ataee8, Abdol Ali Ebrahimi7, Masoumeh Rezaei Moshaei9, Ali Asghar Ahmadi10. 1. Centre for collective, reflection & implementation of ideas, Undersecretary for Research and Technology, Ministry of Health and Medical Education, Tehran, Iran. 2. North Research Center, Pasteur Institute of Iran, Amol, Iran ; 17th Shahrivar Hospital, Mazandaran University of Medical Sciences, Amol, Iran. 3. Iran University of Medical Sciences, School of Paramedicine, Cellular and Molecular Research Center, Tehran, Iran. 4. Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Babol, Iran. 5. Young Researchers and Elite Club, Sari Branch, Islamic Azad University, Sari, Iran. 6. Imam Reza Hospital, Mazandaran University of Medical Sciences, Amol, Iran. 7. Shabid Beheshti University of Medical Sciences, Tehran, Iran. 8. Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran. 9. Department of Plant Breeding and Biotechnology, Agricultural sciences & Natural Resources University of Sari, Iran. 10. North Research Center, Pasteur Institute of Iran, Amol, Iran.
Abstract
OBJECTIVES: To elucidate the possible ways by which hydroxyurea molecules affect globin chain (α or β-like) synthesis. METHODS: A total of 23 thalassemia intermedia patients (13 male and 10 female) aged between 5 and 26 years were treated for five months with 15 mg/(kg·day) of hydroxyurea. Hemoglobins electrophoresis and globin chain electrophoresis was performed on each sample at different time points before and during the treatment. RESULTS: Fetal hemoglobin increased significantly in most patients and average episodes of transfusion decreased. Both Gγ and Aγ-globin chains increased significantly and α-globin:Nonα-globin chain as well as Gγ-globin:Aγ globin chains ratios decreased. CONCLUSIONS: Improvement in α:non-α ratio and consequent decrease of free α-globin chain might be the cause of beneficial effects of hydroxyurea therapy. Two patients who felt better didn't show significant increase in their fetal hemoglobin level, and this is in contradiction with the hypothesis claiming that the HbF level increase is the cause of such therapeutic effect. In spite of the unclear mechanism of action of this drug, hydroxyurea therapy had noticeable impacts on thalassemia intermedia and also sickle cell disease and even patients suffering from thalassemia major.
OBJECTIVES: To elucidate the possible ways by which hydroxyurea molecules affect globin chain (α or β-like) synthesis. METHODS: A total of 23 thalassemia intermediapatients (13 male and 10 female) aged between 5 and 26 years were treated for five months with 15 mg/(kg·day) of hydroxyurea. Hemoglobins electrophoresis and globin chain electrophoresis was performed on each sample at different time points before and during the treatment. RESULTS: Fetal hemoglobin increased significantly in most patients and average episodes of transfusion decreased. Both Gγ and Aγ-globin chains increased significantly and α-globin:Nonα-globin chain as well as Gγ-globin:Aγ globin chains ratios decreased. CONCLUSIONS: Improvement in α:non-α ratio and consequent decrease of free α-globin chain might be the cause of beneficial effects of hydroxyurea therapy. Two patients who felt better didn't show significant increase in their fetal hemoglobin level, and this is in contradiction with the hypothesis claiming that the HbF level increase is the cause of such therapeutic effect. In spite of the unclear mechanism of action of this drug, hydroxyurea therapy had noticeable impacts on thalassemia intermedia and also sickle cell disease and even patients suffering from thalassemia major.
Authors: Mohsen S Elalfy; Amira A M Adly; Eman A Ismail; Yasmine I Elhenawy; Islam R Elghamry Journal: Eur J Haematol Date: 2013-10-05 Impact factor: 2.997