ArticleJournal of cancer research and clinical oncology2019
5-Azacytidine modulates CpG methylation levels of EZH2 and NOTCH1 in myelodysplastic syndromes.
Article in Journal of cancer research and clinical oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 25 citations in OpenAlex.
- Rewriting nuclear epigenetic scripts in mitochondrial diseases as a strategy for heteroplasmy control.EMBO molecular medicine · 2025Article
- Fetal hemoglobin induction in azacytidine responders enlightens methylation patterns related to blast clearance in higher-risk MDS and CMML.Clinical epigenetics · 2024Article
- Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms.Blood advances · 2023Article
- Genomic landscape of myelodysplastic/myeloproliferative neoplasm can predict response to hypomethylating agent therapy.Leukemia & lymphoma · 2022Article
- Low-Dose 5-Aza and DZnep Alleviate Acute Graft-Frontiers in immunology · 2022Article
- Review
- Low Plasma Citrate Levels and Specific Transcriptional Signatures Associated with Quiescence of CD34Cancers · 2021Article
- Unravelling the Epigenome of Myelodysplastic Syndrome: Diagnosis, Prognosis, and Response to Therapy.Cancers · 2020Review
- Noncoding RNAs and Their Response Predictive Value in Azacitidine-treated Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-related Changes.Cancer genomics & proteomicsArticle
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMolecular mechanisms of response to hypomethylating agents in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) still remain largely unknown. Therefore, the effects of 5-Azacytidine (Aza) on clonal architecture and DNA methylation were investigated in this study.
methodsUsing next-generation sequencing (NGS), 30 myeloid leukemia-associated genes were analyzed in 15 MDS/CMML patients with excellent response to Aza. Effects on methylation levels were analyzed by quantitative methylation analysis using pyrosequencing for the global methylation marker LINE-1 in patients and myeloid cell lines. Various myeloid cell lines and a healthy cohort were screened for methylation levels in 23 genes. Selected targets were verified on the MDS/CMML cohort.
resultsThe study presented here showed a stable variant allele frequency and stable global methylation levels in responding patients. A significant demethylation of EZH2 and NOTCH1 was revealed in patients with Aza response.
conclusionsA response to Aza is not associated with eradication of malignant clones, but rather with a stabilization of the clonal architecture. We suggest changes in CpG methylation levels of EZH2 and NOTCH1 as potential targets of epigenetic response to Aza treatment which may also serve as useful biomarkers after clinical evaluation.
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