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.