期刊
JOURNAL OF HEMATOLOGY & ONCOLOGY
卷 12, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13045-019-0757-y
关键词
Super-enhancers; Enhancer; Epigenetics; Hematologic malignancies; BET inhibitor; Combination therapy
资金
- National Research Foundation Singapore
- Singapore Ministry of Education under its Research Centres of Excellence initiative
- NMRC Clinician-Scientist IRG Grant [CNIG11nov38]
- NMRC
- RNA Biology Center at CSI Singapore, NUS - Singapore Ministry of Education [MOE2014-T3-1-006]
Super-enhancers (SEs) in a broad range of human cell types are large clusters of enhancers with aberrant high levels of transcription factor binding, which are central to drive expression of genes in controlling cell identity and stimulating oncogenic transcription. Cancer cells acquire super-enhancers at oncogene and cancerous phenotype relies on these abnormal transcription propelled by SEs. Furthermore, specific inhibitors targeting SEs assembly and activation have offered potential targets for treating various tumors including hematological malignancies. Here, we first review the identification, functional significance of SEs. Next, we summarize recent findings of SEs and SE-driven gene regulation in normal hematopoiesis and hematologic malignancies. The importance and various modes of SE-mediated MYC oncogene amplification are illustrated. Finally, we highlight the progress of SEs as selective therapeutic targets in basic research and clinical trials. Some open questions regarding functional significance and future directions of targeting SEs in the clinic will be discussed too.
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