title: Elucidation of the EP defect in Diamond-Blackfan anemia by characterization and prospective isolation of human EPs.
abstract: Diamond-Blackfan anemia (DBA) is a disorder characterized by a selective defect in erythropoiesis. Delineation of the precise defect is hampered by a lack of markers that define cells giving rise to erythroid burst- and erythroid colony-forming unit (BFU-E and CFU-E) colonies, the clonogenic assays that quantify early and late erythroid progenitor (EEP and LEP) potential, respectively. By combining flow cytometry, cell-sorting, and single-cell clonogenic assays, we identified Lin(-)CD34(+)CD38(+)CD45RA(-)CD123(-)CD71(+)CD41a(-)CD105(-)CD36(-) bone marrow cells as EEP giving rise to BFU-E, and Lin(-)CD34(+/-)CD38(+)CD45RA(-)CD123(-)CD71(+)CD41a(-)CD105(+)CD36(+) cells as LEP giving rise to CFU-E, in a hierarchical fashion. We then applied these definitions to DBA and identified that, compared with controls, frequency, and clonogenicity of DBA, EEP and LEP are significantly decreased in transfusion-dependent but restored in corticosteroid-responsive patients. Thus, both quantitative and qualitative defects in erythroid progenitor (EP) contribute to defective erythropoiesis in DBA. Prospective isolation of defined EPs will facilitate more incisive study of normal and aberrant erythropoiesis.
authors.affiliation: Centre for Haematology, Department of Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom;
authors.forename: Deena
authors.initials: D
authors.lastname: Iskander
authors.affiliation: Centre for Haematology, Department of Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom;
authors.forename: Bethan
authors.initials: B
authors.lastname: Psaila
authors.affiliation: Centre for Haematology, Department of Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom; Imperial Molecular Pathology Laboratory, Imperial College Healthcare National Health Service Trust and Academic Health Sciences Centre, Hammersmith Hospital, London, United Kingdom;
authors.forename: Gareth
authors.initials: G
authors.lastname: Gerrard
authors.affiliation: Centre for Haematology, Department of Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom;
authors.forename: Aristeidis
authors.initials: A
authors.lastname: Chaidos
authors.affiliation: Centre for Haematology, Department of Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom; Imperial Molecular Pathology Laboratory, Imperial College Healthcare National Health Service Trust and Academic Health Sciences Centre, Hammersmith Hospital, London, United Kingdom;
authors.forename: Hui
authors.initials: H
authors.lastname: En Foong
authors.affiliation: Department of Paediatric Haematology and Bone Marrow Transplantation, Imperial College Healthcare National Health Service Trust, London, United Kingdom; and.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Harrington
authors.affiliation: Department of Paediatric Haematology and Bone Marrow Transplantation, Imperial College Healthcare National Health Service Trust, London, United Kingdom; and.
authors.forename: Leena C
authors.initials: LC
authors.lastname: Karnik
authors.affiliation: Department of Paediatrics, Children's Hospital and Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University and John Radcliffe Hospital, Headington, Oxford, United Kingdom.
authors.forename: Irene
authors.initials: I
authors.lastname: Roberts
authors.affiliation: Department of Paediatric Haematology and Bone Marrow Transplantation, Imperial College Healthcare National Health Service Trust, London, United Kingdom; and.
authors.forename: Josu
authors.initials: J
authors.lastname: de la Fuente
authors.affiliation: Centre for Haematology, Department of Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom;
authors.forename: Anastasios
authors.initials: A
authors.lastname: Karadimitris
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D000071063:Endoglin; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D004920:Erythropoiesis; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000235:genetics; D050989:GATA2 Transcription Factor / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018955:CD36 Antigens; C064206:ENG protein, human; D000071063:Endoglin; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D011956:Receptors, Cell Surface