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

Hamaguchi, Isao LU ; Ooka, Andreas LU ; Brun, Ann LU ; Richter, Johan LU ; Dahl, Niklas and Karlsson, Stefan LU (2002) In Blood 100(8). p.2724-2731
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 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... (More)
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) (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
100
issue
8
pages
2724 - 2731
publisher
American Society of Hematology
external identifiers
  • wos:000178519100011
  • pmid:12351378
  • scopus:0037108191
ISSN
1528-0020
language
English
LU publication?
yes
id
7196586b-edde-4bbf-b241-d39b2fcb3391 (old id 110162)
alternative location
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
date added to LUP
2007-07-11 11:53:46
date last changed
2017-08-13 03:38:33
@article{7196586b-edde-4bbf-b241-d39b2fcb3391,
  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 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)},
  author       = {Hamaguchi, Isao and Ooka, Andreas and Brun, Ann and Richter, Johan and Dahl, Niklas and Karlsson, Stefan},
  issn         = {1528-0020},
  language     = {eng},
  number       = {8},
  pages        = {2724--2731},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia.},
  volume       = {100},
  year         = {2002},
}