Novel players in β-thalassemia dyserythropoiesis and new therapeutic strategies.
Paris, France. In Curr Opin Hematol, Feb 2016
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.
A Child With Dyserythropoietic Anemia and Megakaryocyte Dysplasia Due to a Novel 5'UTR GATA1s Splice Mutation.
Indianapolis, United States. In Pediatr Blood Cancer, Jan 2016
We show that (i) this constellation of hematopoietic abnormalities was due to a germline mutation within the 5' untranslated region (5'UTR) of globin transcription factor 1 (GATA1); (ii) the mutation impaired a 5'UTR GATA1 splicing site, with promoted production of the shortened GATA1 isoform lacking the N-terminus; and (iii) expression of the GATA1 N-terminus is restricted to erythroblasts and megakaryocytes in normal marrow, consistent with the patient's abnormal erythropoiesis and megakaryopoiesis.
Altered translation of GATA1 in Diamond-Blackfan anemia.
Boston, United States. In Nat Med, 2014
Here, we identify mutations in GATA1, encoding the critical hematopoietic transcription factor GATA-binding protein-1, that reduce levels of full-length GATA1 protein and cause DBA in rare instances.