<i>In Vitro</i> Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia Syndromes
Defective hemoglobin production and ineffective erythropoiesis contribute to the pathophysiology of thalassemia syndromes. Previous studies in the field of erythropoiesis mainly focused on the severe forms of thalassemia, such as β-thalassemia major, while mechanisms underlying the pathogenesis of o...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/18/5356 |
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| author | Woratree Kaewsakulthong Thunwarat Suriyun Sukanya Chumchuen Usanarat Anurathapan Suradej Hongeng Suthat Fucharoen Orapan Sripichai |
| author_facet | Woratree Kaewsakulthong Thunwarat Suriyun Sukanya Chumchuen Usanarat Anurathapan Suradej Hongeng Suthat Fucharoen Orapan Sripichai |
| author_sort | Woratree Kaewsakulthong |
| collection | DOAJ |
| description | Defective hemoglobin production and ineffective erythropoiesis contribute to the pathophysiology of thalassemia syndromes. Previous studies in the field of erythropoiesis mainly focused on the severe forms of thalassemia, such as β-thalassemia major, while mechanisms underlying the pathogenesis of other thalassemia syndromes remain largely unexplored. The current study aimed to investigate the intrinsic pathophysiological properties of erythroid cells derived from the most common forms of thalassemia diseases, including α-thalassemia (hemoglobin H and hemoglobin H-Constant Spring diseases) and β-thalassemia (homozygous β<sup>0</sup>-thalassemia and β<sup>0</sup>-thalassemia/hemoglobin E diseases), under an identical <i>in vitro</i> erythroid culture system. Cell proliferation capacity, differentiation velocity, cell death, as well as globin synthesis and the expression levels of erythropoiesis modifying factors were determined. Accelerated expansion was found in erythroblast cells derived from all types of thalassemia, with the highest degree in β<sup>0</sup>-thalassemia/hemoglobin E. Likewise, all types of thalassemia showed limited erythroid cell differentiation, but each of them manifested varying degrees of erythroid maturation arrest corresponding with the clinical severity. Robust induction of HSP70 transcripts, an erythroid maturation-related factor, was found in both α- and β-thalassemia erythroid cells. Increased cell death was distinctly present only in homozygous β<sup>0</sup>-thalassemia erythroblasts and associated with the up-regulation of pro-apoptotic (Caspase 9, BAD, and MTCH1) genes and down-regulation of the anti-apoptotic BCL-XL gene. |
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| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T23:37:30Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-e849e75de93c420fa9a98dad85658d4e2023-11-23T16:59:19ZengMDPI AGJournal of Clinical Medicine2077-03832022-09-011118535610.3390/jcm11185356<i>In Vitro</i> Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia SyndromesWoratree Kaewsakulthong0Thunwarat Suriyun1Sukanya Chumchuen2Usanarat Anurathapan3Suradej Hongeng4Suthat Fucharoen5Orapan Sripichai6Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandFaculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandFaculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandFaculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandThalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhonpathom 73710, ThailandThalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhonpathom 73710, ThailandDefective hemoglobin production and ineffective erythropoiesis contribute to the pathophysiology of thalassemia syndromes. Previous studies in the field of erythropoiesis mainly focused on the severe forms of thalassemia, such as β-thalassemia major, while mechanisms underlying the pathogenesis of other thalassemia syndromes remain largely unexplored. The current study aimed to investigate the intrinsic pathophysiological properties of erythroid cells derived from the most common forms of thalassemia diseases, including α-thalassemia (hemoglobin H and hemoglobin H-Constant Spring diseases) and β-thalassemia (homozygous β<sup>0</sup>-thalassemia and β<sup>0</sup>-thalassemia/hemoglobin E diseases), under an identical <i>in vitro</i> erythroid culture system. Cell proliferation capacity, differentiation velocity, cell death, as well as globin synthesis and the expression levels of erythropoiesis modifying factors were determined. Accelerated expansion was found in erythroblast cells derived from all types of thalassemia, with the highest degree in β<sup>0</sup>-thalassemia/hemoglobin E. Likewise, all types of thalassemia showed limited erythroid cell differentiation, but each of them manifested varying degrees of erythroid maturation arrest corresponding with the clinical severity. Robust induction of HSP70 transcripts, an erythroid maturation-related factor, was found in both α- and β-thalassemia erythroid cells. Increased cell death was distinctly present only in homozygous β<sup>0</sup>-thalassemia erythroblasts and associated with the up-regulation of pro-apoptotic (Caspase 9, BAD, and MTCH1) genes and down-regulation of the anti-apoptotic BCL-XL gene.https://www.mdpi.com/2077-0383/11/18/5356thalassemiahemoglobinglobinerythropoiesisapoptosiscell death |
| spellingShingle | Woratree Kaewsakulthong Thunwarat Suriyun Sukanya Chumchuen Usanarat Anurathapan Suradej Hongeng Suthat Fucharoen Orapan Sripichai <i>In Vitro</i> Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia Syndromes Journal of Clinical Medicine thalassemia hemoglobin globin erythropoiesis apoptosis cell death |
| title | <i>In Vitro</i> Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia Syndromes |
| title_full | <i>In Vitro</i> Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia Syndromes |
| title_fullStr | <i>In Vitro</i> Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia Syndromes |
| title_full_unstemmed | <i>In Vitro</i> Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia Syndromes |
| title_short | <i>In Vitro</i> Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia Syndromes |
| title_sort | i in vitro i study of ineffective erythropoiesis in thalassemia diverse intrinsic pathophysiological features of erythroid cells derived from various thalassemia syndromes |
| topic | thalassemia hemoglobin globin erythropoiesis apoptosis cell death |
| url | https://www.mdpi.com/2077-0383/11/18/5356 |
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