The Molecular Basis of Normal Erythroid/Megakaryocyte Development and Mechanisms of Epigenetic/Transcriptional Deregulation Leading to Erythroleukemia and Thalassaemia

Abstract

The recent introduction of high-throughput sequencing technology has now provided a very broad picture of the chromatin landscape and transcription factor binding throughout the genome in many cell types, including the different haematopoietic lineages. The epigenetic machinery affecting DNA methylation and histone modification has been well characterised, and large scale screening for inhibitors has already led to the production of specific drugs used for treating patients. Moreover, it appears that many epigenetic regulators are mutated in various diseases, particularly in the haematopoietic compartment. I discuss here the accessible models used to study erythropoiesis and megakaryopoiesis and their associated transcription and epigenetic programme. Finally, I will describe the current approaches used for epigenetic therapy in myeloid malignancies and haemoglobinopathies such as thalassaemia.