IOX1 Fails to Reduce α-Globin and Mediates γ-Globin Silencing in Adult β<sup>0</sup>-Thalassemia/Hemoglobin E Erythroid Progenitor Cells
Issued Date
2022-08-01
Resource Type
ISSN
0301472X
eISSN
18732399
Scopus ID
2-s2.0-85135536052
Pubmed ID
35839944
Journal Title
Experimental Hematology
Volume
112-113
Start Page
9
End Page
14.e7
Rights Holder(s)
SCOPUS
Bibliographic Citation
Experimental Hematology Vol.112-113 (2022) , 9-14.e7
Suggested Citation
Khamphikham P., Wongborisuth C., Pornprasert S., Tantiworawit A., Tangprasittipap A., Songdej D., Hongeng S. IOX1 Fails to Reduce α-Globin and Mediates γ-Globin Silencing in Adult β<sup>0</sup>-Thalassemia/Hemoglobin E Erythroid Progenitor Cells. Experimental Hematology Vol.112-113 (2022) , 9-14.e7. 14.e7. doi:10.1016/j.exphem.2022.07.004 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83651
Title
IOX1 Fails to Reduce α-Globin and Mediates γ-Globin Silencing in Adult β<sup>0</sup>-Thalassemia/Hemoglobin E Erythroid Progenitor Cells
Author's Affiliation
Other Contributor(s)
Abstract
The accumulation of unbound α-globin chains in red blood cells is a crucial pathophysiology of β-thalassemia. IOX1 (5-carboxy-8-hydroxyquinoline) is a broad-spectrum 2-oxoglutarate (2OG)-dependent oxygenase inhibitor that can reduce α-globin mRNA expression in human cord blood erythroid progenitor cells. Therefore, IOX1 has been proposed as a potential compound for β-thalassemia treatment through the decrease in α-globin chain synthesis. However, there is no empirical evidence regarding the consequences of IOX1 in β-thalassemia. In this study, the therapeutic effects of IOX1 were investigated in β0-thalassemia/hemoglobin E (HbE) erythroid progenitor cells during in vitro erythropoiesis. The results indicated that IOX1 had no impact on α-globin gene expression, but it led instead to significant decreases in γ-globin and fetal hemoglobin (HbF, α2γ2) production without affecting well-known globin regulators: KLF1, BCL11A, LRF, and GATA1. In addition, differential mRNA expression of several genes in the hypoxia response pathway revealed the induction of EGLN1, the PHD2-encoding gene, as a result of IOX1 treatment. These findings suggested that IOX1 fails to lower α-globin gene expression; on the contrary, it mediates γ-globin and HbF silencing in β0-thalassemia/HbE erythroid progenitor cells. Because of the negative correlation of EGLN1 and γ-globin gene expression after IOX1 treatment, repurposing IOX1 to study the hypoxia response pathway and γ-globin regulation may provide beneficial information for β-thalassemia.