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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 β 0 -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, α 2 γ 2 ) 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 β 0 -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., Competing Interests: Conflict of Interest Disclosure The authors declare no competing interests., (Copyright © 2022 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

A large novel 44.6 kb deletion named α 0 -thalassemia Chiang Rai (-- CR ) was first described in the individuals with uncommon Hb Bart's hydrops fetalis and HbH disease. This study aimed to develop a real-time gap PCR and melt curve analysis for the detection of -- CR and investigate its frequency in northern Thailand. Among 4,952 blood samples, the assay was performed in 525 samples with a mean corpuscular volume (MCV) < 80 fL, HbA 2 < 3.5%, HbA 2 +E < 25%, and negative for common deletional α 0 -thalassemia -- SEA and -- THAI . The developed method showed T m values of 85.8 ± 0.0 °C and 91.5 ± 0.1 °C, which were specific for -- CR and wild-type alleles, respectively. Nine (0.18% of 4,952 or 1.71% of 525) were positive for -- CR , in which two were HbH disease and the rest were heterozygous for -- CR . This study demonstrated the success of real-time gap PCR with melt curve analysis for -- CR diagnosis. Additionally, the prevalence of -- CR in the northern Thai population was comparable to -- THAI . Thus, this study implies the importance of -- CR -thalassemia -- 0 -thalassemia -- CR diagnosis in this region.

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