Different methylation signatures at diagnosis in patients with high-risk myelodysplastic syndromes and secondary acute myeloid leukemia predict azacitidine response and longer survival

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• dc.contributor.author Cabezón, Marta
• dc.contributor.author Arenillas Rocha, Leonor
• dc.contributor.author Zamora, Lurdes
• dc.contributor.author CETLAM Group
• dc.date.accessioned 2021-06-14T07:40:26Z
• dc.date.available 2021-06-14T07:40:26Z
• dc.date.issued 2021
• dc.description.abstract Background: Epigenetic therapy, using hypomethylating agents (HMA), is known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy and/or allogeneic stem cell transplantation. However, response rates to HMA are low and there is an unmet need in finding prognostic and predictive biomarkers of treatment response and overall survival. We performed global methylation analysis of 75 patients with high-risk MDS and secondary AML who were included in CETLAM SMD-09 protocol, in which patients received HMA or intensive treatment according to age, comorbidities and cytogenetic. Results: Unsupervised analysis of global methylation pattern at diagnosis did not allow patients to be differentiated according to the cytological subtype, cytogenetic groups, treatment response or patient outcome. However, after a supervised analysis we found a methylation signature defined by 200 probes, which allowed differentiating between patients responding and non-responding to azacitidine (AZA) treatment and a different methylation pattern also defined by 200 probes that allowed to differentiate patients according to their survival. On studying follow-up samples, we confirmed that AZA decreases global DNA methylation, but in our cohort the degree of methylation decrease did not correlate with the type of response. The methylation signature detected at diagnosis was not useful in treated samples to distinguish patients who were going to relapse or progress. Conclusions: Our findings suggest that in a subset of specific CpGs, altered DNA methylation patterns at diagnosis may be useful as a biomarker for predicting AZA response and survival.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cabezón M, Malinverni R, Bargay J, Xicoy B, Marcé S, Garrido A, et al. Different methylation signatures at diagnosis in patients with high-risk myelodysplastic syndromes and secondary acute myeloid leukemia predict azacitidine response and longer survival. Clin Epigenetics. 2021 Jan 14; 13(1): 9. DOI: 10.1186/s13148-021-01002-y
• dc.identifier.doi http://dx.doi.org/10.1186/s13148-021-01002-y
• dc.identifier.issn 1868-7075
• dc.identifier.uri http://hdl.handle.net/10230/47862
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.rights Copyright © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Azacitidine
• dc.subject.keyword DNA methylation
• dc.subject.keyword Epigenetic drugs
• dc.subject.keyword Hypomethylating agents
• dc.subject.keyword Myelodysplastic syndromes
• dc.subject.keyword Prognostic factors
• dc.subject.keyword Secondary acute myeloid leukemia
• dc.title Different methylation signatures at diagnosis in patients with high-risk myelodysplastic syndromes and secondary acute myeloid leukemia predict azacitidine response and longer survival
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion