Novel players in β-thalassemia dyserythropoiesis and new therapeutic strategies

Current Opinion in Hematology
Jean-Benoit ArletGeneviève Courtois

Abstract

The review provides an overview of recent data regarding the molecular players in β-thalassemia dyserythropoiesis and the corresponding therapeutic implications. 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. 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 polych...Continue Reading

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Citations

Aug 2, 2016·BioMed Research International·Lan HuangTian Bai
Sep 24, 2016·Expert Review of Proteomics·Jean-Benoît ArletGeneviève Courtois
Nov 29, 2016·Asian Pacific Journal of Tropical Medicine·Kamonlak LeecharoenkiatDuncan R Smith
Feb 26, 2021·Current Opinion in Hematology·Wassim El NemerSara El Hoss
Aug 29, 2021·Transfusion·Ashutosh LalElliott Vichinsky
Aug 29, 2020·Haematologica·Sara El HossWassim El Nemer

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