Department of Molecular Medicine, Biotechnology Laboratories, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy.
PLoS One. 2013;8(1):e54723. doi: 10.1371/journal.pone.0054723. Epub 2013 Jan 24.
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.
罗米司亭（AMG531）是一种血小板生成素（TPO）受体激动剂，与内源性 TPO 没有同源性，已被用于治疗免疫性血小板减少症（ITP）患者。尽管在临床实践中使用了 TPO 模拟物，但它们对巨核细胞功能影响的机制仍不清楚。
方法/主要发现：在这个项目中，我们利用了我们实验室长期建立的体外人模型来研究从人脐带血衍生祖细胞中巨核细胞的发育，我们证明了增加 AMG531 的剂量（100 至 2000ng/ml）会导致巨核细胞增殖的逐渐增加，同时巨核细胞的倍性和延伸血小板的能力下降。最重要的是，这些巨核细胞功能的差异似乎与 AKT 磷酸化的调节有关。
结论/意义：总的来说，我们的结果为 AMG531 对巨核细胞功能的影响的机制和剂量相关的相关性提供了新的见解。
