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Blood, 15 October 2002, Vol. 100, No. 8, pp. 2724-2731
GENE THERAPY
Gene transfer improves erythroid development in ribosomal protein
S19-deficient Diamond-Blackfan anemia
Isao Hamaguchi,
Andreas Ooka,
Ann Brun,
Johan Richter,
Niklas Dahl, and
Stefan Karlsson
From the Molecular Medicine and Gene Therapy, Institute
of Laboratory Medicine, Lund University Hospital, Sweden; and the
Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala
University Hospital, Sweden.
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.
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