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The (patho)physiology of megakaryocytopoiesis: from thrombopoietin in diagnostics and therapy to ex vivo generated cellular products
Author(s) -
Tijssen M. R.,
Van Der Schoot C. E.,
Voermans C.,
Zwaginga J. J.
Publication year - 2004
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/j.1741-6892.2004.00500.x
Subject(s) - medicine , hematology , megakaryocytopoiesis , medical laboratory , ex vivo , thrombopoietin , pathology , haematopoiesis , in vivo , stem cell , biology , microbiology and biotechnology , genetics
The height of the normal level of blood platelets (150–350 × 10 9 /l) and their short life span (approximately 10 days) explain their production rate of 150 × 10 6 /min. Thrombopoietin (Tpo) is the key growth factor in this production (reviewed in [1] ). Tpo consists of a 153 amino acids long amino-terminal receptorbinding domain and a 179 amino acids carboxy-terminal domain, which is involved in its secretion and protection from proteolysis. The Tpo receptor, Mpl, was discovered in 1992 [2] and is expressed on haematopoietic stem cells (HSCs; CD34 + ), the large polyploid megakaryocyte (MK; platelet progenitor) and platelets themselves [3]. Though genetic elimination of Mpl and Tpo in mice was shown to lead to a strong reduction (85%) of platelet numbers (reviewed in [4]), some platelets are still formed. While synergy with Tpo has been described for SCF [5], effective platelet formation might also depend on factors like SDF-1 and FGF-4. Upregulation of adhesion molecules by these factors enhances late megakaryocytic development and platelet formation by growth promoting interactions between MKs and marrow cells [6].