Gene transfer improves erythroid development in ribosomal protein S19–deficient Diamond-Blackfan anemia

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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 theRPS19 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 withRPS19 gene mutations. Overexpression of theRPS19 transgene increased the number of erythroid colonies by almost 3-fold. High expression levels of the RPS19transgene 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 RPS19gene is feasible.