TY - JOUR
T1 - High Doses of Romiplostim Induce Proliferation and Reduce Proplatelet Formation by Human Megakaryocytes
AU - Currao, Manuela
AU - Balduini, Carlo L.
AU - Balduini, Alessandra
PY - 2013/1/30
Y1 - 2013/1/30
N2 - Background: Romiplostim (AMG531) is a Thrombopoietin (TPO) receptor agonist with no homology with the endogenous TPO that has been used to treat patients affected by immune thrombocytopenia (ITP). Despite the use of TPO mimetics in the clinical practice, the mechanisms underlying their impact on megakaryocyte function is still unknown. Methodology/Principal Findings: In this project we took advantage of an in vitro human model, that we have established in our laboratory for long time to study megakaryocyte development from human cord blood-derived progenitor cells, and we demonstrated that increasing doses of AMG531 (100 to 2000 ng/mL) determine a progressive increase of megakaryocyte proliferation with a parallel decrease in megakaryocyte ploidy and capacity of extending proplatelets. Most importantly, these differences in megakaryocyte function seemed to be correlated to modulation of AKT phosphorylation. Conclusions/Significance: Overall our results shed new light on the mechanisms and on the relevance of dosage related to AMG531 impact on megakaryocyte function.
AB - Background: Romiplostim (AMG531) is a Thrombopoietin (TPO) receptor agonist with no homology with the endogenous TPO that has been used to treat patients affected by immune thrombocytopenia (ITP). Despite the use of TPO mimetics in the clinical practice, the mechanisms underlying their impact on megakaryocyte function is still unknown. Methodology/Principal Findings: In this project we took advantage of an in vitro human model, that we have established in our laboratory for long time to study megakaryocyte development from human cord blood-derived progenitor cells, and we demonstrated that increasing doses of AMG531 (100 to 2000 ng/mL) determine a progressive increase of megakaryocyte proliferation with a parallel decrease in megakaryocyte ploidy and capacity of extending proplatelets. Most importantly, these differences in megakaryocyte function seemed to be correlated to modulation of AKT phosphorylation. Conclusions/Significance: Overall our results shed new light on the mechanisms and on the relevance of dosage related to AMG531 impact on megakaryocyte function.
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U2 - 10.1371/journal.pone.0054723
DO - 10.1371/journal.pone.0054723
M3 - Article
C2 - 23359807
AN - SCOPUS:84872837314
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 1
M1 - e54723
ER -