Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia

Abhishek A. Singh; Francesca Petraglia; Angela Nebbioso; Guoqiang Yi; Mariarosaria Conte; Sergio Valente; Amit Mandoli; Lucia Scisciola; Rik Lindeboom; Hinri Kerstens; Eva M. Janssen-Megens; Farzin Pourfarzad; Ehsan Habibi; Kim Berentsen; Bowon Kim; Colin Logie; Simon Heath; Albertus T.J. Wierenga; Laura Clarke; Paul Flicek; Joop H. Jansen; Taco Kuijpers; Marie Laure Yaspo; Veronique Della Valle; Olivier Bernard; Ivo Gut; Edo Vellenga; Hendrik G. Stunnenberg; Antonello Mai; Lucia Altucci; Joost H.A. Martens

doi:10.18632/oncotarget.25429

Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia

Abhishek A. Singh, Francesca Petraglia, Angela Nebbioso, Guoqiang Yi, Mariarosaria Conte, Sergio Valente, Amit Mandoli, Lucia Scisciola, Rik Lindeboom, Hinri Kerstens, Eva M. Janssen-Megens, Farzin Pourfarzad, Ehsan Habibi, Kim Berentsen, Bowon Kim, Colin Logie, Simon Heath, Albertus T.J. Wierenga, Laura Clarke, Paul FlicekJoop H. Jansen, Taco Kuijpers, Marie Laure Yaspo, Veronique Della Valle, Olivier Bernard, Ivo Gut, Edo Vellenga, Hendrik G. Stunnenberg, Antonello Mai, Lucia Altucci, Joost H.A. Martens

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

12 Citations (Scopus)

Résumé

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 highrisk 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.

langue originale	Anglais
Pages (de - à)	25647-25660
Nombre de pages	14
journal	Oncotarget
Volume	9
Numéro de publication	39
Les DOIs	https://doi.org/10.18632/oncotarget.25429
état	Publié - 22 mai 2018
Modification externe	Oui

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10.18632/oncotarget.25429

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Singh, A. A., Petraglia, F., Nebbioso, A., Yi, G., Conte, M., Valente, S., Mandoli, A., Scisciola, L., Lindeboom, R., Kerstens, H., Janssen-Megens, E. M., Pourfarzad, F., Habibi, E., Berentsen, K., Kim, B., Logie, C., Heath, S., Wierenga, A. T. J., Clarke, L., ... Martens, J. H. A. (2018). Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia. Oncotarget, 9(39), 25647-25660. https://doi.org/10.18632/oncotarget.25429

@article{ab1e66140c974cd3bcbe215a286c7b83,

title = "Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia",

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 highrisk 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.",

keywords = "Acute promyelocytic leukemia (APL), Epi-drugs, Epigenome, High-risk APL, PML-RARA",

author = "Singh, {Abhishek A.} and Francesca Petraglia and Angela Nebbioso and Guoqiang Yi and Mariarosaria Conte and Sergio Valente and Amit Mandoli and Lucia Scisciola and Rik Lindeboom and Hinri Kerstens and Janssen-Megens, {Eva M.} and Farzin Pourfarzad and Ehsan Habibi and Kim Berentsen and Bowon Kim and Colin Logie and Simon Heath and Wierenga, {Albertus T.J.} and Laura Clarke and Paul Flicek and Jansen, {Joop H.} and Taco Kuijpers and Yaspo, {Marie Laure} and {Della Valle}, Veronique and Olivier Bernard and Ivo Gut and Edo Vellenga and Stunnenberg, {Hendrik G.} and Antonello Mai and Lucia Altucci and Martens, {Joost H.A.}",

note = "Publisher Copyright: {\textcopyright} Singh et al.",

year = "2018",

month = may,

day = "22",

doi = "10.18632/oncotarget.25429",

language = "English",

volume = "9",

pages = "25647--25660",

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Singh, AA, Petraglia, F, Nebbioso, A, Yi, G, Conte, M, Valente, S, Mandoli, A, Scisciola, L, Lindeboom, R, Kerstens, H, Janssen-Megens, EM, Pourfarzad, F, Habibi, E, Berentsen, K, Kim, B, Logie, C, Heath, S, Wierenga, ATJ, Clarke, L, Flicek, P, Jansen, JH, Kuijpers, T, Yaspo, ML, Della Valle, V, Bernard, O, Gut, I, Vellenga, E, Stunnenberg, HG, Mai, A, Altucci, L & Martens, JHA 2018, 'Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia', Oncotarget, VOL. 9, Numéro 39, p. 25647-25660. https://doi.org/10.18632/oncotarget.25429

TY - JOUR

T1 - Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia

AU - Singh, Abhishek A.

AU - Petraglia, Francesca

AU - Nebbioso, Angela

AU - Yi, Guoqiang

AU - Conte, Mariarosaria

AU - Valente, Sergio

AU - Mandoli, Amit

AU - Scisciola, Lucia

AU - Lindeboom, Rik

AU - Kerstens, Hinri

AU - Janssen-Megens, Eva M.

AU - Pourfarzad, Farzin

AU - Habibi, Ehsan

AU - Berentsen, Kim

AU - Kim, Bowon

AU - Logie, Colin

AU - Heath, Simon

AU - Wierenga, Albertus T.J.

AU - Clarke, Laura

AU - Flicek, Paul

AU - Jansen, Joop H.

AU - Kuijpers, Taco

AU - Yaspo, Marie Laure

AU - Della Valle, Veronique

AU - Bernard, Olivier

AU - Gut, Ivo

AU - Vellenga, Edo

AU - Stunnenberg, Hendrik G.

AU - Mai, Antonello

AU - Altucci, Lucia

AU - Martens, Joost H.A.

PY - 2018/5/22

Y1 - 2018/5/22

N2 - 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 highrisk 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.

AB - 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 highrisk 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.

KW - Acute promyelocytic leukemia (APL)

KW - Epi-drugs

KW - Epigenome

KW - High-risk APL

KW - PML-RARA

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DO - 10.18632/oncotarget.25429

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