Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by a specific deficiency in erythroid progenitors. Since some patients with DBA develop a reduction in thrombocytes and granulocytes with age, we asked whether multipotent hematopoietic progenitors from DBA patients had normal proliferative capacity in liquid expansion cultures. CD34(+) cells derived from DBA patients showed deficient proliferation in liquid culture containing IL-3, IL-6, and SCF. Single CD34(+) CD38(-) cells from DBA patients exhibited deficient proliferation recruitment in a limiting dilution assay containing IL-3, IL-6, SCF, Tpo, FL, and G-CSF or containing IL-3, IL-6, and SCF. Our findings suggest that the underlying hematopoietic defect in DBA may not be limited to the erythroid lineage. Since a fraction of DBA patients have a deficiency in ribosomal protein S19 (RPS19), we constructed lentiviral vectors containing the RPS19 gene for overexpression in hematopoietic progenitors from RPS19-deficient DBA patients. Enforced expression of the RPS19 transgene improved the proliferation of CD34(+) cells from DBA patients with RPS19 mutation. Similarly, enforced expression of RPS19 improved erythroid development of RPS19-deficient hematopoietic progenitors as determined by colony assays and erythroid differentiation cultures. These findings suggest that gene therapy for RPS19-deficient DBA is feasible.
Diamond - Blackfan anemia ( DBA ) is a congenital bone marrow failure syndrome characterized by a specific deficiency in erythroid progenitors . Since some patients with DBA develop a reduction in thrombocytes and granulocytes with age , we asked whether multipotent hematopoietic progenitors from DBA patients had normal proliferative capacity in liquid expansion cultures . CD34(+ ) cells derived from DBA patients showed deficient proliferation in liquid culture containing IL-3 , IL-6 , and SCF . Single CD34(+ ) CD38(- ) cells from DBA patients exhibited deficient proliferation recruitment in a limiting dilution assay containing IL-3 , IL-6 , SCF , Tpo , FL , and G - CSF or containing IL-3 , IL-6 , and SCF . Our findings suggest that the underlying hematopoietic defect in DBA may not be limited to the erythroid lineage . Since a fraction of DBA patients have a deficiency in ribosomal protein S19 ( RPS19 ) , we constructed lentiviral vectors containing the RPS19 gene for overexpression in hematopoietic progenitors from RPS19-deficient DBA patients . Enforced expression of the RPS19 transgene improved the proliferation of CD34(+ ) cells from DBA patients with RPS19 mutation . Similarly , enforced expression of RPS19 improved erythroid development of RPS19-deficient hematopoietic progenitors as determined by colony assays and erythroid differentiation cultures . These findings suggest that gene therapy for RPS19-deficient DBA 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