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Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia.
- Source :
-
Blood [Blood] 2002 Oct 15; Vol. 100 (8), pp. 2724-31. - Publication Year :
- 2002
-
Abstract
- Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by a specific deficiency in erythroid progenitors. Forty percent of the patients are blood transfusion-dependent. Recent reports show that the ribosomal protein S19 (RPS19) gene is mutated in 25% of all patients with DBA. We constructed oncoretroviral vectors containing the RPS19 gene to develop gene therapy for RPS19-deficient DBA. These vectors were used to introduce the RPS19 gene into CD34(+) bone marrow (BM) cells from 4 patients with DBA with RPS19 gene mutations. Overexpression of the RPS19 transgene increased the number of erythroid colonies by almost 3-fold. High expression levels of the RPS19 transgene improved erythroid colony-forming ability substantially whereas low expression levels had no effect. Overexpression of RPS19 had no detrimental effect on granulocyte-macrophage colony formation. Therefore, these findings suggest that gene therapy for RPS19-deficient patients with DBA using viral vectors that express the RPS19 gene is feasible.
- Subjects :
- Adult
Antigens, CD analysis
Antigens, CD34 analysis
Bone Marrow Cells cytology
Cell Line
Child
Colony-Forming Units Assay
Female
Gene Transfer Techniques
Genetic Vectors
Hematopoietic Stem Cells cytology
Hematopoietic Stem Cells pathology
Humans
Male
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Anemia, Diamond-Blackfan genetics
Anemia, Diamond-Blackfan therapy
Bone Marrow Cells physiology
Bone Marrow Transplantation methods
Hematopoietic Stem Cells physiology
Ribosomal Proteins deficiency
Ribosomal Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 100
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 12351378
- Full Text :
- https://doi.org/10.1182/blood.V100.8.2724