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Pharmacoproteomics Profiling of Plasma From β‐Thalassemia Patients in Response to Hydroxyurea Treatment
Author(s) -
Zohaib Muhammad,
Ansari Saqib H.,
Shamsi Tahir S.,
Zubarev Roman A.,
Zarina Shamshad
Publication year - 2019
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1297
Subject(s) - hemopexin , fetal hemoglobin , thalassemia , haptoglobin , medicine , proteome , blood proteins , transferrin , hemoglobin f , hemoglobinopathy , beta thalassemia , globin , hemoglobin , pharmacology , immunology , hemolytic anemia , biology , bioinformatics , fetus , heme , genetics , pregnancy , biochemistry , enzyme
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 subunit γ‐1, and peroxiredoxin‐2 showing the significant changes. The mechanism of hydroxyurea treatment in β‐thalassemia patients appears to be complex, requiring a large sample size and a longer period of treatment to reveal its details.

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