Gene therapy cures the anemia and lethal bone marrow failure in mouse model for RPS19-deficient Diamond-Blackfan anemia.
Jaako, Pekka LU ; Debnath, Shubhranshu LU ; Olsson, Karin LU ; Modlich, Ute ; Rothe, Michael ; Schambach, Axel ; Flygare, Johan LU and Karlsson, Stefan LU
(2014)
In Haematologica
99(12).
p.1792-1798
- Abstract
- Diamond-Blackfan anemia is a congenital erythroid hypoplasia caused by functional haploinsufficiency of genes encoding ribosomal proteins. Mutations involving the ribosomal protein S19 gene are detected in 25 % of patients. Enforced expression of ribosomal protein S19 improves the overall proliferative capacity, erythroid colony-forming potential and erythroid differentiation of hematopoietic progenitors from ribosomal protein S19-deficient patients in vitro and in vivo following xenotransplantation. However, studies using animal models are needed to assess the therapeutic efficacy and safety of the viral vectors. In the present study we have validated the therapeutic potential of gene therapy using mouse models for ribosomal protein... (More)
- Diamond-Blackfan anemia is a congenital erythroid hypoplasia caused by functional haploinsufficiency of genes encoding ribosomal proteins. Mutations involving the ribosomal protein S19 gene are detected in 25 % of patients. Enforced expression of ribosomal protein S19 improves the overall proliferative capacity, erythroid colony-forming potential and erythroid differentiation of hematopoietic progenitors from ribosomal protein S19-deficient patients in vitro and in vivo following xenotransplantation. However, studies using animal models are needed to assess the therapeutic efficacy and safety of the viral vectors. In the present study we have validated the therapeutic potential of gene therapy using mouse models for ribosomal protein S19-deficient Diamond-Blackfan anemia. Using lentiviral gene transfer we demonstrate that enforced expression of ribosomal protein S19 cures the anemia and lethal bone marrow failure in recipients transplanted with ribosomal protein S19-deficient cells. Furthermore, gene-corrected ribosomal protein S19-deficient cells showed an increased pan-hematopoietic contribution over time compared to untransduced cells without signs of vector-mediated toxicity. Our study provides a proof of principle for the development of clinical gene therapy to cure ribosomal protein 19-deficient Diamond-Blackfan anemia. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4691692
- author
- Jaako, Pekka
LU
; Debnath, Shubhranshu
LU
; Olsson, Karin
LU
; Modlich, Ute
; Rothe, Michael
; Schambach, Axel
; Flygare, Johan
LU
and Karlsson, Stefan
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Haematologica
- volume
- 99
- issue
- 12
- pages
- 7 pages
- publisher
- Ferrata Storti Foundation
- external identifiers
-
- pmid:25216681
- wos:000347016400004
- scopus:84919339897
- pmid:25216681
- ISSN
- 1592-8721
- DOI
- 10.3324/haematol.2014.111195
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Stem Cell Aging (013212073), Division of Molecular Medicine and Gene Therapy (013022010)
- id
- 68c4878a-a554-4f10-b96f-7cdd55be135c (old id 4691692)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25216681?dopt=Abstract
- date added to LUP
- 2016-04-01 11:03:37
- date last changed
- 2022-03-05 01:16:03
@article{68c4878a-a554-4f10-b96f-7cdd55be135c,
abstract = {{Diamond-Blackfan anemia is a congenital erythroid hypoplasia caused by functional haploinsufficiency of genes encoding ribosomal proteins. Mutations involving the ribosomal protein S19 gene are detected in 25 % of patients. Enforced expression of ribosomal protein S19 improves the overall proliferative capacity, erythroid colony-forming potential and erythroid differentiation of hematopoietic progenitors from ribosomal protein S19-deficient patients in vitro and in vivo following xenotransplantation. However, studies using animal models are needed to assess the therapeutic efficacy and safety of the viral vectors. In the present study we have validated the therapeutic potential of gene therapy using mouse models for ribosomal protein S19-deficient Diamond-Blackfan anemia. Using lentiviral gene transfer we demonstrate that enforced expression of ribosomal protein S19 cures the anemia and lethal bone marrow failure in recipients transplanted with ribosomal protein S19-deficient cells. Furthermore, gene-corrected ribosomal protein S19-deficient cells showed an increased pan-hematopoietic contribution over time compared to untransduced cells without signs of vector-mediated toxicity. Our study provides a proof of principle for the development of clinical gene therapy to cure ribosomal protein 19-deficient Diamond-Blackfan anemia.}},
author = {{Jaako, Pekka and Debnath, Shubhranshu and Olsson, Karin and Modlich, Ute and Rothe, Michael and Schambach, Axel and Flygare, Johan and Karlsson, Stefan}},
issn = {{1592-8721}},
language = {{eng}},
number = {{12}},
pages = {{1792--1798}},
publisher = {{Ferrata Storti Foundation}},
series = {{Haematologica}},
title = {{Gene therapy cures the anemia and lethal bone marrow failure in mouse model for RPS19-deficient Diamond-Blackfan anemia.}},
url = {{http://dx.doi.org/10.3324/haematol.2014.111195}},
doi = {{10.3324/haematol.2014.111195}},
volume = {{99}},
year = {{2014}},
}