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Production of beta-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous beta(0)39 thalassemia patients.
- Source :
-
American journal of hematology [Am J Hematol] 2009 Nov; Vol. 84 (11), pp. 720-8. - Publication Year :
- 2009
-
Abstract
- In several types of thalassemia (including beta(0)39-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying beta-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the beta(0)39-thalassemia globin gene under control of the beta-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of beta-globin by K562 cell clones expressing the beta(0)39-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from beta(0)39-thalassemia patients were demonstrated to be able to produce beta-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of beta(0)-thalassemia caused by stop codon mutations. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.
- Subjects :
- Cells, Cultured
Erythroid Precursor Cells cytology
Hemoglobins genetics
Homozygote
Humans
K562 Cells
beta-Globins drug effects
beta-Globins genetics
beta-Thalassemia blood
beta-Thalassemia genetics
Codon, Nonsense
Erythroid Precursor Cells metabolism
Gentamicins pharmacology
Hemoglobins biosynthesis
beta-Globins biosynthesis
beta-Thalassemia drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1096-8652
- Volume :
- 84
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- American journal of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 19810011
- Full Text :
- https://doi.org/10.1002/ajh.21539