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.
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 .
In which syndrome is the RPS19 gene most frequently mutated?
In which syndrome is the RPS19 gene most frequently mutated ?
Diamond-Blackfan Anemia DBA
Diamond-Blackfan Anemia DBA