Proliferation deficiency of multipotent hematopoietic progenitors in ribosomal protein S19 (RPS19)-deficient Diamond-Blackfan anemia improves following RPS19 gene transfer
Hamaguchi, Isao LU ; Flygare, Johan LU ; Nishiura, Hiroshi LU ; Brun, Ann LU ; Ooka, Andreas LU ; Kiefer, Thomas LU ; Ma, Zhi LU ; Dahl, N ; Richter, Johan LU and Karlsson, Stefan LU
(2003)
In Molecular Therapy
7(5).
p.613-622
- Abstract
- 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, FIL, and G-CSF or containing IL-3, IL-6, and SCF. Our findings suggest that the underlying hematopoietic... (More)
- 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, FIL, 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/311958
- author
- Hamaguchi, Isao
LU
; Flygare, Johan
LU
; Nishiura, Hiroshi
LU
; Brun, Ann
LU
; Ooka, Andreas
LU
; Kiefer, Thomas
LU
; Ma, Zhi
LU
; Dahl, N
; Richter, Johan
LU
and Karlsson, Stefan
LU
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- hematopoietic progenitors, lentiviral vectors, gene therapy, Diamond-Blackfan anemia
- in
- Molecular Therapy
- volume
- 7
- issue
- 5
- pages
- 613 - 622
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:12718904
- wos:000182645800009
- scopus:0038190929
- ISSN
- 1525-0024
- DOI
- 10.1016/S1525-0016(03)00091-1
- language
- English
- LU publication?
- yes
- id
- a4771b6c-1150-427f-a70a-c2fe50a441ba (old id 311958)
- date added to LUP
- 2016-04-01 12:06:39
- date last changed
- 2022-01-26 22:57:25
@article{a4771b6c-1150-427f-a70a-c2fe50a441ba,
abstract = {{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, FIL, 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.}},
author = {{Hamaguchi, Isao and Flygare, Johan and Nishiura, Hiroshi and Brun, Ann and Ooka, Andreas and Kiefer, Thomas and Ma, Zhi and Dahl, N and Richter, Johan and Karlsson, Stefan}},
issn = {{1525-0024}},
keywords = {{hematopoietic progenitors; lentiviral vectors; gene therapy; Diamond-Blackfan anemia}},
language = {{eng}},
number = {{5}},
pages = {{613--622}},
publisher = {{Nature Publishing Group}},
series = {{Molecular Therapy}},
title = {{Proliferation deficiency of multipotent hematopoietic progenitors in ribosomal protein S19 (RPS19)-deficient Diamond-Blackfan anemia improves following RPS19 gene transfer}},
url = {{http://dx.doi.org/10.1016/S1525-0016(03)00091-1}},
doi = {{10.1016/S1525-0016(03)00091-1}},
volume = {{7}},
year = {{2003}},
}