Expert Reviews in Molecular Medicine

Review Article

Normal and malignant megakaryopoiesis

Qiang Wena1, Benjamin Goldensona1 and John D. Crispinoa1 c1

a1 Division of Hematology/Oncology, Northwestern University, Chicago, IL, USA

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.

Correspondence

c1 Corresponding author: John D. Crispino, Division of Hematology/Oncology, Northwestern University, 303 East Superior Street, Lurie 5-113, Chicago, IL 60611, USA. E-mail: j-crispino@northwestern.edu