Advances in megakaryocytopoiesis and thrombopoiesis: From bench to bedside

Varda R. Deutsch, Aaron Tomer

Research output: Contribution to journalReview articlepeer-review

80 Scopus citations

Abstract

Megakaryocytopoiesis involves the commitment of haematopoietic stem cells, proliferation and terminal differentiation of megakaryocytic progenitors (MK-p) and maturation of megakaryocytes (MKs) to produce functional platelets. This complex process occurs in specialized niches in the bone marrow where MKs align adjacent to vascular endothelial cells, form proplatelet projections and release platelets into the circulation. Thrombopoietin (THPO, TPO) is the primary growth factor for the MK lineage and necessary at all stages of development. THPO is constitutively produced in the liver, and binds to MPL (c-Mpl) receptor on platelets and MKs. This activates a cascade of signalling molecules, which induce transcription factors to drive MK development and thrombopoiesis. Decreased turnover rate and platelet number result in increased levels of free THPO, which induces a concentration-dependant compensatory response of marrow-MKs to enhance platelet production. Newly developed thrombopoietic agents operating via MPL receptor facilitate platelet production in thrombocytopenic states, primarily immune thrombocytopenia. Other drugs are available for attenuating malignant thrombocytosis. Herein, we review the regulation of megakaryocytopoiesis and platelet production in normal and disease states, and the innovative drugs and therapeutic modalities to stimulate or decrease thrombopoiesis.

Original languageEnglish
Pages (from-to)778-793
Number of pages16
JournalBritish Journal of Haematology
Volume161
Issue number6
DOIs
StatePublished - 1 Jun 2013

Keywords

  • Megakaryocytes
  • Megakaryocytopoiesis
  • Mimetics
  • Thrombopoiesis
  • Thrombopoietin

ASJC Scopus subject areas

  • Hematology

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