Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia
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- dc.contributor.author Singh, Abhishek A.
- dc.contributor.author Heath, Simon
- dc.contributor.author Gut, Ivo Glynne
- dc.contributor.author Martens, Joost H.A.
- dc.date.accessioned 2019-11-28T08:29:05Z
- dc.date.available 2019-11-28T08:29:05Z
- dc.date.issued 2018
- dc.description.abstract 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.
- dc.format.mimetype application/pdf
- dc.identifier.citation Singh AA, Petraglia F, Nebbioso A, Yi G, Conte M, Valente S et al. Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia. Oncotarget. 2018; 9(39):25647-25660. DOI 10.18632/oncotarget.25429
- dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.25429
- dc.identifier.issn 1949-2553
- dc.identifier.uri http://hdl.handle.net/10230/43024
- dc.language.iso eng
- dc.publisher Impact Journals
- dc.relation.ispartof Oncotarget. 2018; 9(39):25647-25660
- dc.rights © Singh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0) (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/3.0/
- dc.subject.keyword Epigenome
- dc.subject.keyword Acute promyelocytic leukemia (APL)
- dc.subject.keyword PML-RARA
- dc.subject.keyword High-risk APL
- dc.subject.keyword Epi-drugs
- dc.title Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion