Publication: Association of the Degree of Erythroid Expansion and Maturation Arrest with the Clinical Severity of β<sup>0</sup>-Thalassemia/Hemoglobin e Patients
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Issued Date
2021-11-01
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ISSN
14219662
00015792
00015792
Other identifier(s)
2-s2.0-85115664759
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Mahidol University
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SCOPUS
Bibliographic Citation
Acta Haematologica. Vol.144, No.6 (2021), 660-671
Suggested Citation
Thunwarat Suriyun, Woratree Kaewsakulthong, Pinyaphat Khamphikham, Sukanya Chumchuen, Suradej Hongeng, Suthat Fucharoen, Orapan Sripichai Association of the Degree of Erythroid Expansion and Maturation Arrest with the Clinical Severity of β<sup>0</sup>-Thalassemia/Hemoglobin e Patients. Acta Haematologica. Vol.144, No.6 (2021), 660-671. doi:10.1159/000518310 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/77729
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Title
Association of the Degree of Erythroid Expansion and Maturation Arrest with the Clinical Severity of β<sup>0</sup>-Thalassemia/Hemoglobin e Patients
Abstract
Introduction: β-Thalassemia/hemoglobin E represents one-half of all the clinically severe β-thalassemias worldwide. Despite similar genetic backgrounds, patients show clinical heterogeneity ranging from nearly asymptomatic to transfusion-dependent thalassemia. The underlying disease modifying factors remain largely obscure. Methods: To elucidate the correlation between ineffective erythropoiesis and β0-thalassemia/hemoglobin E (HbE) disease severity, in vitro culture of erythroid cells derived from patients with different clinical symptoms was established. Cell proliferation, viability, and differentiation were investigated. To identify potential molecular mechanisms leading to the arrested erythroid maturation, the expression levels of erythropoiesis modifying factors were measured. Results: The β0-thalassemia/HbE cells exhibited enhanced proliferation, limited differentiation, and impaired erythroid terminal maturation but did not show accelerated erythroblast differentiation and increased cell death. Erythroblasts derived from mild patients showed the highest proliferation rate with a faster cell division time, while erythroblasts derived from severe patients displayed extremely delayed erythroid maturation. Downregulation of growth differentiation factor 11 and FOXO3a was observed in mild β0-thalassemia/HbE erythroblasts, while upregulation of heat shock protein 70 and activin receptor 2A was revealed in severe erythroblasts. Discussion/Conclusion: The degree of erythroid expansion and maturation arrest contributes to the severity of β0-thalassemia/HbE patients, accounting for the disease heterogeneity. The findings suggest a restoration of erythroid maturation as a promising targeted therapy for severe patients.