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Advances in megakaryocytopoiesis and thrombopoiesis: from bench to bedside
Author(s) -
Deutsch Varda R.,
Tomer Aaron
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12328
Subject(s) - thrombopoiesis , megakaryocytopoiesis , thrombopoietin , haematopoiesis , platelet , megakaryocyte , microbiology and biotechnology , immunology , bone marrow , thrombocytosis , biology , progenitor cell , romiplostim , cancer research , stem cell , medicine
Summary Megakaryocytopoiesis involves the commitment of haematopoietic stem cells, proliferation and terminal differentiation of megakaryocytic progenitors ( MK ‐p) and maturation of megakaryocytes ( MK s) to produce functional platelets. This complex process occurs in specialized niches in the bone marrow where MK s 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‐ M pl) receptor on platelets and MK s. 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‐ MK s 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.