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• W2334344396 abstract "Purpose of review The review provides an overview of recent data regarding the molecular players in β-thalassemia dyserythropoiesis and the corresponding therapeutic implications. Recent findings β-thalassemia dyserythropoiesis is characterized by four steps: expansion of erythroid progenitors, accelerated erythroid differentiation until the polychromatophilic stage, maturation arrest, and apoptosis at the polychromatophilic stage. Excess α-globin chains are the primary culprit in the disease, but the link between this excess and ineffective erythropoiesis has only recently been established. Important recent advances in understanding the molecular determinants involved in two critical steps of dyserythropoiesis are paving the way to new alternative targets for the treatment of this disease. Summary Growth differentiation factor 11 (GDF11) blockade increases the apoptosis of erythroblasts with excess α-chains by upregulating Fas-ligand in late basophilic and polychromatophilic erythroblasts, thereby decreasing cell expansion (step 1). Blocking GDF11 alleviates anemia in a mouse model of β-thalassemia and also in humans, most likely by promoting cells of ‘good’ erythroblastic lineage containing an α-/non-α-globin chain ratio of close to 1. Maturation arrest at the polychromatophilic stage (step 3) is associated with the depletion of GATA binding protein 1 (GATA-1) from the nucleus, which results from cytoplasmic sequestration of heat shock protein 70 (HSP70) by α-globin chains. Small molecules disrupting the HSP70/α-globin complex in the cytoplasm or decreasing HSP70 nuclear export might increase the nuclear localization of HSP70, thereby protecting GATA-1 and alleviating anemia. Finally, increasing the serum levels of hepcidin or transferrin alleviates anemia and dyserythropoiesis by diminishing iron uptake by erythroblasts in mouse models." @default.
• W2334344396 created "2016-06-24" @default.
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• W2334344396 date "2016-05-01" @default.
• W2334344396 modified "2023-10-15" @default.
• W2334344396 title "Novel players in β-thalassemia dyserythropoiesis and new therapeutic strategies" @default.
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• W2334344396 doi "https://doi.org/10.1097/moh.0000000000000231" @default.
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