Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia.
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.
D000328:Adult; D029503:Anemia, Diamond-Blackfan / Q000235:genetics* / Q000628:therapy*; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002460:Cell Line; D002648:Child; D003114:Colony-Forming Units Assay; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D006801:Humans; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000172:deficiency* / Q000235:genetics*; D014162:Transfection
D015703:Antigens, CD; D018952:Antigens, CD34; D012269:Ribosomal Proteins; C040343:ribosomal protein S19