Balduini Alessandra, Raslova Hana, Di Buduo Christian A, Donada Alessandro, Ballmaier Matthias, Germeshausen Manuela, Balduini Carlo L
University of Pavia, Pavia, Italy; IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
INSERM UMR 1170, Gustave Roussy Cancer Campus, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.
Eur J Med Genet. 2018 Nov;61(11):715-722. doi: 10.1016/j.ejmg.2018.01.014. Epub 2018 Mar 13.
Inherited thrombocytopenias (ITs) are a heterogeneous group of disorders characterized by low platelet count resulting in impaired hemostasis. Patients can have spontaneous hemorrhages and/or excessive bleedings provoked by hemostatic challenges as trauma or surgery. To date, ITs encompass 32 different rare monogenic disorders caused by mutations of 30 genes. This review will focus on the major discoveries that have been made in the last years on the diagnosis, treatment and molecular mechanisms of ANKRD26-Related Thrombocytopenia and MYH9-Related Diseases. Furthermore, we will discuss the use a Thrombopoietin mimetic as a novel approach to treat the thrombocytopenia in these patients. We will propose the use of a new 3D bone marrow model to study the mechanisms of action of these drugs and to test their efficacy and safety in patients. The overall purpose of this review is to point out that important progresses have been made in understanding the pathogenesis of ANKRD26-Related Thrombocytopenia and MYH9-Related Diseases and new therapeutic approaches have been proposed and tested. Future advancement in this research will rely in the development of more physiological models to study the regulation of human platelet biogenesis, disease mechanisms and specific pharmacologic targets.
遗传性血小板减少症（ITs）是一组异质性疾病，其特征为血小板计数低，导致止血功能受损。患者可能会出现自发性出血和/或因创伤或手术等止血挑战引发的过度出血。迄今为止，ITs包括由30个基因的突变引起的32种不同的罕见单基因疾病。本综述将聚焦于近年来在ANKRD26相关血小板减少症和MYH9相关疾病的诊断、治疗及分子机制方面取得的主要发现。此外，我们将讨论使用血小板生成素模拟物作为治疗这些患者血小板减少症的一种新方法。我们将提议使用一种新的三维骨髓模型来研究这些药物的作用机制，并在患者中测试其疗效和安全性。本综述的总体目的是指出，在理解ANKRD26相关血小板减少症和MYH9相关疾病的发病机制方面已取得重要进展，并且已提出并测试了新的治疗方法。该研究的未来进展将依赖于开发更多生理模型，以研究人类血小板生成的调节、疾病机制和特定的药理学靶点。
