New Platelet-Boosting Drugs May Be On The Way

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British Journal of Haematology

Volume 134 Page 453 - September 2006

doi:10.1111/j.1365-2141.2006.06215.x

Volume 134 Issue 5

Megakaryocyte development and platelet production

Varda R. Deutsch1 and Tomer2,3

Summary

Megakaryocytopoiesis involves the commitment of haematopoietic stem

cells, and the proliferation, maturation and terminal differentiation

of the megakaryocytic progenitors.

Circulating levels of thrombopoietin (TPO), the primary growth-factor

for the megakaryocyte (MK) lineage, induce concentration–dependent

proliferation and maturation of MK progenitors by binding to the c-

Mpl receptor and signalling induction. Decreased platelet turnover

rates results in increased concentration of free TPO, enabling the

compensatory response of marrow MKs to increased platelet production.

C-Mpl activity is orchestrated by a complex cascade of signalling

molecules that induces the action of specific transcription factors

to drive MK proliferation and maturation. Mature MKs form proplatelet

projections that are fragmented into circulating particles.

Newly developed thrombopoietic agents operating via c-Mpl receptor

may prove useful in supporting platelet production in

thrombocytopenic state. Herein, we review the regulation of

megakaryocytopoiesis and platelet production in normal and disease

state, and the new approaches to thrombopoietic therapy.