Megakaryocytic transcription factors in disease and leukemia

Abstract

An understanding of the transcriptional regulation of megakaryopoiesis has lagged behind that of other hematopoietic lineages due to the rarity of these cells and the relatively recent development of systems to culture large numbers of megakaryocytes. However, significant progress has been made over the past few decades resulting in the identification of many key transcription factors involved in megakaryocyte specification and maturation. A number of important principles have emerged including physical and functional interactions among a core set of transcription factors including GATA, ETS, and RUNX family members, cross antagonistic network interactions with key erythroid-specific factors in cell fate determination of bipotential erythroid-megakaryocytic progenitor cells, and a surprising overlap with hematopoietic stem cell transcriptional regulators. A high proportion of genes encoding megakaryocytic transcription factors are mutated in human thrombopoiesis disorders, and a number of these are associated with leukemia predisposition. This chapter reviews the current knowledge about transcription factors involved in megakaryopoiesis, how they interact, and how their activities are influenced by cell signaling events. It also highlights the important role that dysregulation of these factors play in certain human platelet biogenesis disorders and leukemogenesis.