Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia.
Publication year
2018Source
Oncotarget, 9, 39, (2018), pp. 25647-25660ISSN
Publication type
Article / Letter to editor
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Organization
Molecular Biology
Proteomics and Chromatin Biology
Laboratory Medicine
Journal title
Oncotarget
Volume
vol. 9
Issue
iss. 39
Page start
p. 25647
Page end
p. 25660
Subject
Molecular Biology; Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life Sciences; Proteomics and Chromatin BiologyAbstract
Epigenomic alterations have been associated with both pathogenesis and progression of cancer. Here, we analyzed the epigenome of two high-risk APL (hrAPL) patients and compared it to non-high-risk APL cases. Despite the lack of common genetic signatures, we found that human hrAPL blasts from patients with extremely poor prognosis display specific patterns of histone H3 acetylation, specifically hyperacetylation at a common set of enhancer regions. In addition, unique profiles of the repressive marks H3K27me3 and DNA methylation were exposed in high-risk APLs. Epigenetic comparison with low/intermediate-risk APLs and AMLs revealed hrAPL-specific patterns of histone acetylation and DNA methylation, suggesting these could be further developed into markers for clinical identification. The epigenetic drug MC2884, a newly generated general HAT/EZH2 inhibitor, induces apoptosis of high-risk APL blasts and reshapes their epigenomes by targeting both active and repressive marks. Together, our analysis uncovers distinctive epigenome signatures of hrAPL patients, and provides proof of concept for use of epigenome profiling coupled to epigenetic drugs to 'personalize' precision medicine.
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- Academic publications [238441]
- Electronic publications [122508]
- Faculty of Medical Sciences [90373]
- Faculty of Science [34986]
- Open Access publications [97504]
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