ArticleGenome biology2014
DNMT inhibitors reverse a specific signature of aberrant promoter DNA methylation and associated gene silencing in AML.
Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 66 citations in OpenAlex.
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- Abnormal regulation of miR-29b-ID1 signaling is involved in the process of decitabine resistance in leukemia cells.Cell cycle (Georgetown, Tex.) · 2023Article
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- Recurrent transcriptional responses in AML and MDS patients treated with decitabine.Experimental hematology · 2022Article
- ImmuMethy, a database of DNA methylation plasticity at a single cytosine resolution in human blood and immune cells.Database : the journal of biological databases and curation · 2022Article
- Urgent need for consistent standards in functional enrichment analysis.PLoS computational biology · 2022Article
- Epigenetic Regulation of Breast Cancer Stem Cells Contributing to Carcinogenesis and Therapeutic Implications.International journal of molecular sciences · 2021Review
- A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks.Epigenetics · 2021Article
- Anticancer Effects of I-BET151, an Inhibitor of Bromodomain and Extra-Terminal Domain Proteins.Frontiers in oncology · 2021Review
- A novel treatment regimen of granulocyte colony-stimulating factor combined with ultra-low-dose decitabine and low-dose cytarabine in older patients with acute myeloid leukemia and myelodysplastic syndromes.Therapeutic advances in hematology · 2021Article
- Hypomethylating Agents and Immunotherapy: Therapeutic Synergism in Acute Myeloid Leukemia and Myelodysplastic Syndromes.Frontiers in oncology · 2021Review
- DNMT1 as a therapeutic target in pancreatic cancer: mechanisms and clinical implications.Cellular oncology (Dordrecht, Netherlands) · 2020Review
- Identification of methylation states of DNA regions for Illumina methylation BeadChip.BMC genomics · 2020Article
- Prognostic role of ACTL10 in Cytogenetic Normal Acute Myeloid Leukemia.Journal of Cancer · 2020Article
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- Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia.Biomarker insights · 2019Review
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- Chromatin Regulation by HP1γ Contributes to Survival of 5-Azacytidine-Resistant Cells.Frontiers in pharmacology · 2018Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMyelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are neoplastic disorders of hematopoietic stem cells. DNA methyltransferase inhibitors, 5-azacytidine and 5-aza-2'-deoxycytidine (decitabine), benefit some MDS/AML patients. However, the role of DNA methyltransferase inhibitor-induced DNA hypomethylation in regulation of gene expression in AML is unclear.
resultsWe compared the effects of 5-azacytidine on DNA methylation and gene expression using whole-genome single-nucleotide bisulfite-sequencing and RNA-sequencing in OCI-AML3 cells. For data analysis, we used an approach recently developed for discovery of differential patterns of DNA methylation associated with changes in gene expression, that is tailored to single-nucleotide bisulfite-sequencing data (Washington University Interpolated Methylation Signatures). Using this approach, we find that a subset of genes upregulated by 5-azacytidine are characterized by 5-azacytidine-induced signature methylation loss flanking the transcription start site. Many of these genes show increased methylation and decreased expression in OCI-AML3 cells compared to normal hematopoietic stem and progenitor cells. Moreover, these genes are preferentially upregulated by decitabine in human primary AML blasts, and control cell proliferation, death, and development.
conclusionsOur approach identifies a set of genes whose methylation and silencing in AML is reversed by DNA methyltransferase inhibitors. These genes are good candidates for direct regulation by DNA methyltransferase inhibitors, and their reactivation by DNA methyltransferase inhibitors may contribute to therapeutic activity.
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