Publication: Increased erythropoiesis of β-thalassaemia/Hb E proerythroblasts is mediated by high basal levels of ERK1/2 activation
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Issued Date
2009-09-01
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ISSN
13652141
00071048
00071048
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2-s2.0-68949201206
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Mahidol University
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SCOPUS
Bibliographic Citation
British Journal of Haematology. Vol.146, No.5 (2009), 557-568
Suggested Citation
Tirawat Wannatung, Pathrapol Lithanatudom, Amporn Leecharoenkiat, Saovaros Svasti, Suthat Fucharoen, Duncan R. Smith Increased erythropoiesis of β-thalassaemia/Hb E proerythroblasts is mediated by high basal levels of ERK1/2 activation. British Journal of Haematology. Vol.146, No.5 (2009), 557-568. doi:10.1111/j.1365-2141.2009.07794.x Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/27938
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Title
Increased erythropoiesis of β-thalassaemia/Hb E proerythroblasts is mediated by high basal levels of ERK1/2 activation
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Abstract
β-thalassaemia is one of the most common inherited anaemias, arising from a partial or complete loss of β-globin chain synthesis. In severe cases, marked bone marrow erythroid hyperplasia, believed to result from erythropoietin (EPO)-mediated feedback from the anaemic condition is common, however, as yet, no study has investigated EPO-mediated signal transduction in thalassaemic erythroid cells. Using proerythroblasts generated from peripheral blood circulating CD34+ haematopoietic progenitor cells, the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERKs) pathway was examined under conditions of steady state growth, cytokine deprivation and post-EPO stimulation. Levels of cellular cyclic adenosine monophosphate (cAMP) and Ca2+ were determined as was the degree of erythroid expansion. A significantly higher basal level of phosphorylation of ERK1/2 was observed in β-thalassaemia/Hb E proerythroblasts as compared to normal controls, which was coupled with significantly higher levels of both cAMP and Ca2+. Modulation of either cAMP or Ca2+ or direct inhibition of MAPK/ERK kinase (MEK) reduced basal levels of ERK1/2 phosphorylation, as well as significantly reducing the level of erythroid expansion. These results suggest that, in contrast to current models, hyper proliferation of β-thalassaemia/Hb E proerythroblasts is an intrinsic process driven by higher basal levels of ERK1/2 phosphorylation resulting from deregulation of levels of cAMP and Ca 2+. © 2009 Blackwell Publishing Ltd.