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

Summary, in English

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. (Blood. 2002;100:2724-2731)

• Författare: Isao Hamaguchi; Andreas Ooka; Ann Brun; Johan Richter; Niklas Dahl; Stefan Karlsson
• Avdelning/ar: Avdelningen för molekylärmedicin och genterapi
• Publiceringsår: 2002
• Språk: Engelska
• Sidor: 2724-2731
• Publikation/Tidskrift/Serie: Blood
• Volym: 100
• Issue: 8
• Länkar: http://bloodjournal.hematologylibrary.org/cgi/content/full/100/8/2724; http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12351378&dopt=Abstract
• Dokumenttyp: Artikel i tidskrift
• Förlag: American Society of Hematology
• Ämne: Hematology
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1528-0020