Ineffective erythropoiesis in β-thalassemia major is due to apoptosis at the polychromatophilic normoblast stage
| Autor: | Timothy C. Fisher, Herbert J. Meiselman, Alan L. Hiti, Licheng Zeng, Liesl A Mathias, Punam Malik, Kenneth I. Weinberg |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Ineffective erythropoiesis Cancer Research Cellular differentiation Population CD34 Gene Expression Antigens CD34 Apoptosis Bone Marrow Cells Biology CD38 medicine.disease_cause NAD+ Nucleosidase Antigens CD hemic and lymphatic diseases In Situ Nick-End Labeling Genetics medicine Humans Erythropoiesis Glycophorins Progenitor cell ADP-ribosyl Cyclase Child education Molecular Biology Cells Cultured Erythroid Precursor Cells education.field_of_study Membrane Glycoproteins beta-Thalassemia Infant Cell Differentiation Cell Biology Hematology ADP-ribosyl Cyclase 1 Antigens Differentiation Molecular biology medicine.anatomical_structure Child Preschool Immunology Erythrocyte Count Bone marrow |
| Zdroj: | Experimental Hematology. 28:1343-1353 |
| ISSN: | 0301-472X |
| DOI: | 10.1016/s0301-472x(00)00555-5 |
| Popis: | Beta-thalassemia major is characterized by ineffective erythropoiesis, although it is difficult to define the dynamics of this process from the static information revealed by analysis of bone marrow (BM) aspirates. We aimed to study the kinetics of sequential erythroid differentiation in beta-thalassemia major. We isolated the progenitor cells (CD34(+) and CD34(+)CD38(-) cells) from BM of thalassemia major patients and studied in vitro erythropoiesis. This is the first report of an in vitro study in human beta-thalassemia major from purified BM CD34(+) progenitor cells, using erythroid culture conditions, which allow unilineage differentiation to mature enucleated red blood cells. In contrast to normal donors, a high proportion of BM CD34(+) and CD34(+)CD38(-) progenitors from beta-thalassemia major coexpressed the late erythroid lineage-specific protein glycophorin A and generated a higher proportion of erythroid colonies. However, despite the marked increase in erythroid clonogenicity of the progenitor population, erythroid cultures initiated from beta-thalassemia major BM CD34(+) cells expanded 10- to 20-fold less than from normal BM. There were less viable cells during differentiation, specifically after the polychromatophilic normoblast stage. There was a progressive increase in the apoptotic erythroid progeny with differentiation, and apoptosis occurred predominantly at the polychromatophilic normoblast stage. In thalassemia major, BM progenitor cells show increased erythroid clonogenicity, increased expression of late erythroid lineage-specific proteins, and accelerated erythroid differentiation. However, despite the apparent increased erythroid commitment, ineffective erythropoiesis occurs due to apoptosis at the polychromatophil stage. Identification of the differentiation stage at which apoptosis occurs will permit further studies of the underlying mechanisms and target therapeutic strategies to improve red cell production. |
| Databáze: | OpenAIRE |
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