Peeters Karen, Stassen Jean-Marie, Collen Désiré, Van Geet Chris, Freson Kathleen
Center for Molecular and Vascular Biology, University of Leuven, Herestraat 49, Leuven, Belgium.
Drug Discov Today. 2008 Sep;13(17-18):798-806. doi: 10.1016/j.drudis.2008.06.002. Epub 2008 Jul 17.
Thrombocytopenia is a common medical problem. The first generation thrombopoietic agents, recombinant THPO and 'megakaryocyte growth and development factor' (PEG-rHuMGDF) entered clinical trials, but their development was discontinued owing to neutralizing auto-antibodies cross-reacting with endogenous THPO, causing thrombocytopenia in healthy volunteers. Although an approved drug for prevention of severe thrombocytopenia following myelosuppressive chemotherapy (human Interleukin-11) exists, the search for new thrombopoietic agents continued because its use is limited by side effects. Several second generation thrombopoietic factors have entered clinical trials and some new negative regulators of megakaryopoiesis have been found, such as platelet factor 4 (PF4) and the pituitary adenylate cyclase activating polypeptide (PACAP). Their inhibition may be useful in the treatment of thrombocytopenia. This article reviews second generation thrombopoietic factors and those recently discovered regulators of megakaryopoiesis.
血小板减少症是一种常见的医学问题。第一代血小板生成剂，即重组血小板生成素（THPO）和“巨核细胞生长与发育因子”（PEG-rHuMGDF）进入了临床试验，但由于与内源性THPO发生交叉反应的中和性自身抗体导致健康志愿者出现血小板减少症，它们的研发被终止。尽管存在一种已获批用于预防骨髓抑制化疗后严重血小板减少症的药物（人白细胞介素-11），但由于其副作用限制了其使用，因此对新型血小板生成剂的研究仍在继续。几种第二代血小板生成因子已进入临床试验，并且发现了一些新的巨核细胞生成负调节因子，如血小板因子4（PF4）和垂体腺苷酸环化酶激活多肽（PACAP）。它们的抑制作用可能对血小板减少症的治疗有用。本文综述了第二代血小板生成因子以及最近发现的那些巨核细胞生成调节因子。
