Abstract
β-thalassemia/Hb E is a global health issue, which is characterized by a range of clinical symptoms from a mild and asymptomatic anemia to severe disorders that require transfusions from infancy. Pathological mechanisms of the disease involve the excess of unmatched alpha globin and iron overload, leading to ineffective erythropoiesis and ultimately to the premature death of erythroid precursors in bone marrow (BM) and peripheral organs. However, it is unclear as to how BM microenvironment factors contribute to the defective erythropoiesis in β-thalassemia/Hb E patients. Here, we employed mass spectrometry-based comparative proteomics to analyze BM plasma that was collected from six β-thalassemia/Hb E patients and four healthy donors. We identified that the differentially expressed proteins are enriched in secretory or exosome-associated proteins, many of which have putative functions in the oxidative stress response. Using Western blot assay, we confirmed that atypical lipoprotein, Apolipoprotein D (APOD), belonging to the Lipocalin transporter superfamily, was significantly decreased in BM plasma of the tested pediatric β-thalassemia/Hb E patients. Our results highlight that the disease condition of ineffective erythropoiesis and oxidative stress found in BM microenvironment of β-thalassemia/Hb E patients is associated with the impaired expression of APOD protein.
Highlights
Thalassemia is a heterogeneous group of anemias that involve a defective synthesis of mature hemoglobin (Hb)
We report an interesting imbalance protein expression involving oxidative and anti-oxidative processes, which may contribute to ineffective erythropoiesis that is found in β-thalassemia/Hb E patients
The bone marrow (BM) plasma samples were collected from six β-thalassemia/Hb E patients and four healthy donors
Summary
Thalassemia is a heterogeneous group of anemias that involve a defective synthesis of mature hemoglobin (Hb). The pathophysiology of β-thalassemia/Hb E is strongly associated with the excess of unmatched α-globin chain and the mutation of hemoglobin variants [1]. These phenomena are believed to be the etiological factors of an ineffective erythropoiesis in BM causing hemolysis in peripheral circulation [2,3]. These clinical manifestations are derived from chronic anemia and iron overload and are caused by an increased iron absorption in the gastrointestinal tract as well as long-term blood transfusions [3,4].
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