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Normal and malignant megakaryopoiesis

Published online by Cambridge University Press:  21 October 2011

Qiang Wen
Affiliation:
Division of Hematology/Oncology, Northwestern University, Chicago, IL, USA
Benjamin Goldenson
Affiliation:
Division of Hematology/Oncology, Northwestern University, Chicago, IL, USA
John D. Crispino*
Affiliation:
Division of Hematology/Oncology, Northwestern University, Chicago, IL, USA
*
*Corresponding author: John D. Crispino, Division of Hematology/Oncology, Northwestern University, 303 East Superior Street, Lurie 5-113, Chicago, IL 60611, USA. E-mail: [email protected]

Abstract

Megakaryopoiesis is the process by which bone marrow progenitor cells develop into mature megakaryocytes (MKs), which in turn produce platelets required for normal haemostasis. Over the past decade, molecular mechanisms that contribute to MK development and differentiation have begun to be elucidated. In this review, we provide an overview of megakaryopoiesis and summarise the latest developments in this field. Specially, we focus on polyploidisation, a unique form of the cell cycle that allows MKs to increase their DNA content, and the genes that regulate this process. In addition, because MKs have an important role in the pathogenesis of acute megakaryocytic leukaemia and a subset of myeloproliferative neoplasms, including essential thrombocythemia and primary myelofibrosis, we discuss the biology and genetics of these disorders. We anticipate that an increased understanding of normal MK differentiation will provide new insights into novel therapeutic approaches that will directly benefit patients.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2011

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References

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Further reading, resources and contacts

The following recent papers may be of interest to those who want to delve deeper into recent reports of normal and malignant megakaryopoiesis:

Tefferi, A. and Vainchenker, W. (2011) Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. Journal of Clinical Oncology 29, 573-582CrossRefGoogle ScholarPubMed
Verstovsek, S. (2010) Therapeutic potential of Janus-activated kinase-2 inhibitors for the management of myelofibrosis. Clinical Cancer Research 16, 1988-1996CrossRefGoogle ScholarPubMed
Pardanani, A. et al. (2011) JAK inhibitor therapy for myelofibrosis: critical assessment of value and limitations. Leukemia 25, 218-225CrossRefGoogle Scholar
Chen, E. et al. (2010) Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1 signaling. Cancer Cell 18, 524-535CrossRefGoogle ScholarPubMed
Chagraoui, H. et al. (2011) SCL-mediated regulation of the cell-cycle regulator p21 is critical for murine megakaryopoiesis. Blood 118, 723-735.CrossRefGoogle ScholarPubMed
Doré, L. and Crispino, J.D. (2011) Transcription factor networks in erythroid cell and megakaryocyte development. Blood 118, 231-239CrossRefGoogle ScholarPubMed