DNA methylation in normal and malignant hematopoiesis

The study of DNA methylation has been a rapidly expanding field since its dawn in the 1960s. DNA methylation is an epigenetic modification that plays a crucial role in guiding the differentiation of stem cells to their destined lineage, and in maintaining tissue homeostasis. Moreover, aberrant DNA methylation has been well characterized as a significant contributing factor in the pathogenesis of a variety of cancers. Hematopoiesis is a process that is uniquely susceptible to epigenetic changes due to the small pool of actively cycling stem cells that give rise to the entire mature immune–hematopoietic system. Mutations in DNA methyltransferase enzymes have been shown to be initiating events in the development of hematological malignancies such as acute myeloid leukemia and, therefore, have become targets for improved diagnostics and therapy. The spatial and temporal regulation of DNA methylation in the hematopoietic developmental hierarchy is critical to hematopoietic homeostasis. An improved understanding of the roles that DNA methylation plays in normal and malignant hematopoiesis will have a significant impact on the future of regenerative stem cell therapy and clinical treatment of hematopoietic malignancies. This review aims to highlight current developments in the field and prioritize future research directions.