Pharmacoproteomics Profiling of Plasma From β-Thalassemia Patients in Response to Hydroxyurea Treatment

Journal of Clinical Pharmacology
Muhammad ZohaibShamshad Zarina

Abstract

β-Thalassemia is a genetic disorder caused by defects in the β-globin gene resulting in the absence or reduced synthesis of adult hemoglobin (HbA). Hydroxyurea is an effective drug to increase fetal γ-globin (HbF) expression, replacing the missing adult β-globin. The mechanism of HbF induction by hydroxyurea and improvement in clinical symptoms are still poorly understood. In the present study we performed comparative analysis of plasma proteome in pre- and post-hydroxyurea-treated β-thalassemia major transfusion-dependent children (n = 10, mean age = 3.2 years) as well as responders versus nonresponders to hydroxyurea treatment. Plasma was collected before and after 6 months of hydroxyurea treatment, with patients subcategorized on the basis of their response to hydroxyurea. Among 400 identified proteins using a label-free quantitative proteomics approach, 28 proteins were found to be significantly different in pre- versus post-hydroxyurea-treated groups, with transferrin receptor protein-1 being most downregulated and hemopexin and haptoglobin the most upregulated proteins after treatment. In responder versus nonresponder comparison, 26 proteins were found to be differentially expressed, with carbonic anhydrase 1, hemoglobin ...Continue Reading

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Citations

Apr 19, 2019·Expert Review of Proteomics·Conor McCaffertyVera Ignjatovic
Mar 3, 2021·Orphanet Journal of Rare Diseases·Nirmani YasaraSachith Mettananda
Jul 21, 2021·International Journal of Molecular Sciences·Filomena LongoAntonio Piga
Mar 13, 2021·Journal of Pediatric Hematology/oncology·Saqib H AnsariTahir S Shamsi

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