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.
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We thank the members of all laboratories, and M. Guillamot and L. Cimmino for comments and illustrations. Supported by the US National Institutes of Health (1K08CA160647-01 and R01 HL128239 for the Abdel-Wahab laboratory; and RO1CA133379, RO1CA105129, RO1CA149655, 5RO1CA173636, 1RO1CA194923 and R01 CA190509 for the Aifantis laboratory); the National Cancer Institute (R00CA188293-02), the American Society of Hematology, the Zell Foundation and the Chicago Region Physical Science-Oncology Center (all for the Ntziachristos laboratory); the Department of Defense (BM150092 and W81XWH-12-1-0041), the Damon Runyon Foundation, the Edward P. Evans Foundation, the V Foundation, the Starr Foundation, the Josie Robertson Investigator Program and the Pershing Square Sohn Cancer Research Alliance (all for the Abdel-Wahab laboratory); and the Leukemia and Lymphoma Society, the NYSTEM program of the New York State Health Department, The William Lawrence and Blanche Hughes Foundation and the Chemotherapy Foundation (all for the Aifantis laboratory).
The authors declare no competing financial interests.
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Ntziachristos, P., Abdel-Wahab, O. & Aifantis, I. Emerging concepts of epigenetic dysregulation in hematological malignancies. Nat Immunol 17, 1016–1024 (2016). https://doi.org/10.1038/ni.3517
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