Semin Thromb Hemost 2004; 30(4): 389-398
DOI: 10.1055/s-2004-833474
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Molecular Mechanisms of Megakaryocyte Differentiation

Harald Schulze1 , 2 , Ramesh A. Shivdasani1 , 2 , 3
  • 1Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute; Departments of Medicine, Boston, Massachusetts
  • 2Harvard Medical School, Boston, Massachusetts
  • 3Associate Professor of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
Further Information

Publication History

Publication Date:
08 September 2004 (online)

Each bone marrow megakaryocyte (MK) releases thousands of platelets into the circulation, and the underlying molecular and cellular mechanisms recently have received intense scrutiny. Genetic studies are beginning to clarify the mechanisms by which transcription factors help distinguish MK progenitors from other blood cell lineages and subsequently confer unique cellular properties. Other investigations demonstrate that platelets are assembled de novo during a terminal phase of MK differentiation in which the cell extends cytoplasmic projections known as proplatelets. This review focuses on the roles of selected transcription factors with key roles in MK differentiation, and on human and murine models of thrombocytopenia that result from impaired MK differentiation. The findings we review help construct a framework to appreciate thrombopoietic mechanisms in the context of underlying lineage and morphologic transitions. Many of these mechanisms are unique to MKs but appear to rely both on genes that are expressed only in that lineage and others that are expressed widely.

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Ramesh A ShivdasaniM.D. Ph.D. 

Dana-Farber Cancer Institute

One Jimmy Fund Way, Boston, MA 02115

Email: ramesh_shivdasani@dfci.harvard.edu