Mechanisms and therapeutic prospects of thrombopoietin receptor agonists

Research output: Contribution to journalReview article

Abstract

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.

Details

Authors
  • James Bussel
  • Austin Kulasekararaj
  • Nichola Cooper
  • Amit Verma
  • Ulrich Steidl
  • John W. Semple
  • Britta Will
Organisations
External organisations
  • King's College Hospital
  • Hammersmith Hospital
  • Cornell University
  • Yeshiva University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology

Keywords

  • Eltrombopag, Mechanism of action, Megakaryopoiesis, Romiplostim, Thrombocytopenia
Original languageEnglish
Pages (from-to)262-278
JournalSeminars in Hematology
Volume56
Issue number4
Early online date2019 Oct 19
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes