Lysine-specific histone demethylases in normal and malignant hematopoiesis

•Histone demethylases play critical roles in hematopoietic development and lineage commitment•Several histone demethylases have context dependent roles in leukemias•Targeting histone demethylases with small molecule inhibitors is a promising therapeutic approach for treating hematopoietic malignancies

The epigenetic control of gene expression is central to the development of the hematopoietic system and the execution of lineage-specific transcriptional programs. During the last 10 years, mounting evidence has implicated the family of lysine-specific histone demethylases as critical regulators of normal hematopoiesis, whereas their deregulation is found in a broad spectrum of hematopoietic malignancies. Here, we review recent findings on the role of these enzymes in normal and malignant hematopoiesis and highlight how aberrant epigenetic regulation facilitates hematopoietic cell transformation through subversion of cell fate and lineage commitment programs.