Pediatric Hematology/Oncology, Weill Cornell Medicine, New York, NY.
King's College Hospital NHS Foundation Trust, London, UK.
Semin Hematol. 2019 Oct;56(4):262-278. doi: 10.1053/j.seminhematol.2019.09.001. Epub 2019 Oct 19.
The second-generation thrombopoietin (TPO) receptor agonists eltrombopag and romiplostim are potent activators of megakaryopoiesis and represent a growing treatment option for patients with thrombocytopenic hematological disorders. Both TPO receptor agonists have been approved worldwide for the treatment of children and adults with chronic immune thrombocytopenia. In the EU and USA, eltrombopag is approved for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy and in the USA for the first-line treatment of severe aplastic anemia in combination with immunosuppressive therapy. Eltrombopag has also shown efficacy in several other disease settings, for example, chemotherapy-induced thrombocytopenia, selected inherited thrombocytopenias, and myelodysplastic syndromes. While both TPO receptor agonists stimulate TPO receptor signaling and enhance megakaryopoiesis, their vastly different biochemical structures bestow upon them markedly different molecular and functional properties. Here, we review and discuss results from preclinical and clinical studies on the functional and molecular mechanisms of action of this new class of drug.
第二代血小板生成素 (TPO) 受体激动剂艾曲泊帕和罗米司亭是巨核细胞生成的有效激活剂，是血小板减少性血液系统疾病患者的一种不断增加的治疗选择。这两种 TPO 受体激动剂已在全球范围内获得批准，用于治疗慢性免疫性血小板减少症的儿童和成人患者。在欧盟和美国，艾曲泊帕被批准用于治疗对免疫抑制治疗反应不足的重型再生障碍性贫血患者，在美国也被批准与免疫抑制治疗联合用于治疗重型再生障碍性贫血的一线治疗。艾曲泊帕还在其他一些疾病领域显示出疗效，例如化疗诱导的血小板减少症、某些遗传性血小板减少症和骨髓增生异常综合征。虽然这两种 TPO 受体激动剂都能刺激 TPO 受体信号通路并增强巨核细胞生成，但它们截然不同的生化结构赋予它们截然不同的分子和功能特性。在这里，我们综述和讨论了关于这一类新药的作用机制的临床前和临床研究结果。
