Clinic, pathogenic mechanisms and drug testing of two inherited thrombocytopenias, ANKRD26-related Thrombocytopenia and MYH9-related diseases

Eur J Med Genet. 2018 Nov;61(11):715-722. doi: 10.1016/j.ejmg.2018.01.014. Epub 2018 Mar 13.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • Genetic Predisposition to Disease*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Molecular Motor Proteins / genetics*
  • Mutation
  • Myosin Heavy Chains / genetics*
  • Nuclear Proteins / genetics*
  • Thrombocytopenia / drug therapy*
  • Thrombocytopenia / genetics
  • Thrombocytopenia / pathology

Substances

  • ANKRD26 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MYH9 protein, human
  • Molecular Motor Proteins
  • Nuclear Proteins
  • Myosin Heavy Chains