Journal of Translational Medicine 2013-01-01

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

Yinghong He, Gerhard Rank, Miaomiao Zhang, Junyi Ju, Ronghua Liu, Zhen Xu, Fiona Brown, Loretta Cerruti, Chi Ma, Renxiang Tan, Stephen M Jane, Quan Zhao

文献索引：J. Transl. Med. 11 , 14, (2013)

全文：HTML全文

摘要

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.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).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).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.