Emerging concepts of epigenetic dysregulation in hematological malignancies

The past decade brought a revolution in understanding of the structure, topology and disease-inducing lesions of RNA and DNA, fueled by unprecedented progress in next-generation sequencing. This technological revolution has also affected understanding of the epigenome and has provided unique opportunities for the analysis of DNA and histone modifications, as well as the first map of the non-protein-coding genome and three-dimensional (3D) chromosomal interactions. Overall, these advances have facilitated studies that combine genetic, transcriptomics and epigenomics data to address a wide range of issues ranging from understanding the role of the epigenome in development to targeting the transcription of noncoding genes in human cancer. Here we describe recent insights into epigenetic dysregulation characteristic of the malignant differentiation of blood stem cells based on studies of alterations that affect epigenetic complexes, enhancers, chromatin, long noncoding RNAs (lncRNAs), RNA splicing, nuclear topology and the 3D conformation of chromatin.