Premium
Increased erythropoiesis of β‐thalassaemia/Hb E proerythroblasts is mediated by high basal levels of ERK1/2 activation
Author(s) -
Wannatung Tirawat,
Lithanatudom Pathrapol,
Leecharoenkiat Amporn,
Svasti Saovaros,
Fucharoen Suthat,
Smith Duncan R.
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07794.x
Subject(s) - erythropoiesis , basal (medicine) , ineffective erythropoiesis , biology , medicine , anemia , insulin
Summary 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 Ca 2+ 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 Ca 2+ . Modulation of either cAMP or Ca 2+ 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+ .