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Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde

BACKGROUND: Pharmacologic reactivation of fetal hemoglobin expression is a promising strategy for treatment of sickle cell disease and β-thalassemia. The objective of this study was to investigate the effect of the methyl transferase inhibitor adenosine-2’,3’-dialdehyde (Adox) on induction of human...

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Autores principales: He, Yinghong, Rank, Gerhard, Zhang, Miaomiao, Ju, Junyi, Liu, Ronghua, Xu, Zhen, Brown, Fiona, Cerruti, Loretta, Ma, Chi, Tan, Renxiang, Jane, Stephen M, Zhao, Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599103/
https://www.ncbi.nlm.nih.gov/pubmed/23316703
http://dx.doi.org/10.1186/1479-5876-11-14
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author He, Yinghong
Rank, Gerhard
Zhang, Miaomiao
Ju, Junyi
Liu, Ronghua
Xu, Zhen
Brown, Fiona
Cerruti, Loretta
Ma, Chi
Tan, Renxiang
Jane, Stephen M
Zhao, Quan
author_facet He, Yinghong
Rank, Gerhard
Zhang, Miaomiao
Ju, Junyi
Liu, Ronghua
Xu, Zhen
Brown, Fiona
Cerruti, Loretta
Ma, Chi
Tan, Renxiang
Jane, Stephen M
Zhao, Quan
author_sort He, Yinghong
collection PubMed
description BACKGROUND: Pharmacologic reactivation of fetal hemoglobin expression is a promising strategy for treatment of sickle cell disease and β-thalassemia. The objective of this study was to investigate the effect of the methyl transferase inhibitor adenosine-2’,3’-dialdehyde (Adox) on induction of human fetal hemoglobin (HbF) in K562 cells and human hematopoietic progenitor cells. METHODS: Expression levels of human fetal hemoglobin were assessed by northern blot analysis and Real-time PCR. HbF and adult hemoglobin (HbA) content were analyzed using high-performance liquid chromatography (HPLC). DNA methylation levels on human gamma-globin gene promoters were determined using Bisulfite sequence analysis. Enrichment of histone marks on genes was assessed by chromosome immunoprecipitation (ChIP). RESULTS: Adox induced γ-globin gene expression in both K562 cells and in human bone marrow erythroid progenitor cells through a mechanism potentially involving inhibition of protein arginine methyltransferase 5 (PRMT5). CONCLUSIONS: The ability of methyl transferase inhibitors such as Adox to efficiently reactivate fetal hemoglobin expression suggests that these agents may provide a means of reactivating fetal globin expression as a therapeutic option for treating sickle cell disease and β-thalassemia.
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spelling pubmed-35991032013-03-17 Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde He, Yinghong Rank, Gerhard Zhang, Miaomiao Ju, Junyi Liu, Ronghua Xu, Zhen Brown, Fiona Cerruti, Loretta Ma, Chi Tan, Renxiang Jane, Stephen M Zhao, Quan J Transl Med Research BACKGROUND: Pharmacologic reactivation of fetal hemoglobin expression is a promising strategy for treatment of sickle cell disease and β-thalassemia. The objective of this study was to investigate the effect of the methyl transferase inhibitor adenosine-2’,3’-dialdehyde (Adox) on induction of human fetal hemoglobin (HbF) in K562 cells and human hematopoietic progenitor cells. METHODS: Expression levels of human fetal hemoglobin were assessed by northern blot analysis and Real-time PCR. HbF and adult hemoglobin (HbA) content were analyzed using high-performance liquid chromatography (HPLC). DNA methylation levels on human gamma-globin gene promoters were determined using Bisulfite sequence analysis. Enrichment of histone marks on genes was assessed by chromosome immunoprecipitation (ChIP). RESULTS: Adox induced γ-globin gene expression in both K562 cells and in human bone marrow erythroid progenitor cells through a mechanism potentially involving inhibition of protein arginine methyltransferase 5 (PRMT5). CONCLUSIONS: The ability of methyl transferase inhibitors such as Adox to efficiently reactivate fetal hemoglobin expression suggests that these agents may provide a means of reactivating fetal globin expression as a therapeutic option for treating sickle cell disease and β-thalassemia. BioMed Central 2013-01-14 /pmc/articles/PMC3599103/ /pubmed/23316703 http://dx.doi.org/10.1186/1479-5876-11-14 Text en Copyright ©2013 He et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
He, Yinghong
Rank, Gerhard
Zhang, Miaomiao
Ju, Junyi
Liu, Ronghua
Xu, Zhen
Brown, Fiona
Cerruti, Loretta
Ma, Chi
Tan, Renxiang
Jane, Stephen M
Zhao, Quan
Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde
title Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde
title_full Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde
title_fullStr Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde
title_full_unstemmed Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde
title_short Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde
title_sort induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599103/
https://www.ncbi.nlm.nih.gov/pubmed/23316703
http://dx.doi.org/10.1186/1479-5876-11-14
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