ArticleJournal of hematology & oncology2014
Hypermethylation of the alternative AWT1 promoter in hematological malignancies is a highly specific marker for acute myeloid leukemias despite high expression levels.
Article in Journal of hematology & oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Integrated study of DNA methylation and transcriptome: a new perspective for exploring the pathogenesis of Sjögren's syndrome.Epigenetics & chromatin · 2025Article
- TERT promoter methylation predicts overall survival, immune cell infiltration and response to immunotherapy in clear cell renal cell carcinoma.Clinical epigenetics · 2025Article
- The role of imprinting genes' loss of imprints in cancers and their clinical implications.Frontiers in oncology · 2024Review
- Comprehensive analysis of TLX2 in pan cancer as a prognostic and immunologic biomarker and validation in ovarian cancer.Scientific reports · 2023Article
- Identification of cystic fibrosis transmembrane conductance regulator as a prognostic marker for juvenile myelomonocytic leukemia via the whole-genome bisulfite sequencing of monozygotic twins and data mining.Translational pediatrics · 2022Article
- Developmental and Injury-induced Changes in DNA Methylation in Regenerative versus Non-regenerative Regions of the Vertebrate Central Nervous System.BMC genomics · 2022Article
- Long Noncoding RNA Expression Profiling Reveals Upregulation of Uroplakin 1A and Uroplakin 1A Antisense RNA 1 under Hypoxic Conditions in Lung Cancer Cells.Molecules and cells · 2020Article
- Review
- The clinical significance of the alternative Wilms tumor gene overexpression-hypermethylation signature in acute myeloid leukemia.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Article
- Repression of TERRA Expression by Subtelomeric DNA Methylation Is Dependent on NRF1 Binding.International journal of molecular sciences · 2019Article
- WT1 Alternative Splicing: Role of Its Isoforms in Neuroblastoma.Journal of molecular neuroscience : MN · 2017Review
- Distal CpG islands can serve as alternative promoters to transcribe genes with silenced proximal promoters.Genome research · 2017Article
- DNA Methylation Events as Markers for Diagnosis and Management of Acute Myeloid Leukemia and Myelodysplastic Syndrome.Disease markers · 2017Review
- Quantitative assessment of Wilms tumor 1 expression by real-time quantitative polymerase chain reaction in patients with acute myeloblastic leukemia.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2017Article
- Targeting histone methylation for cancer therapy: enzymes, inhibitors, biological activity and perspectives.Journal of hematology & oncology · 2016Review
- Review
- Hidden among the crowd: differential DNA methylation-expression correlations in cancer occur at important oncogenic pathways.Frontiers in genetics · 2015Article
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWilms tumor 1 (WT1) is over-expressed in numerous cancers with respect to normal cells, and has either a tumor suppressor or oncogenic role depending on cellular context. This gene is associated with numerous alternatively spliced transcripts, which initiate from two different unique first exons within the WT1 and the alternative (A)WT1 promoter intervals. Within the hematological system, WT1 expression is restricted to CD34+/CD38- cells and is undetectable after differentiation. Detectable expression of this gene is an excellent marker for minimal residual disease in acute myeloid leukemia (AML), but the underlying epigenetic alterations are unknown.
methodsTo determine the changes in the underlying epigenetic landscape responsible for this expression, we characterized expression, DNA methylation and histone modification profiles in 28 hematological cancer cell lines and confirmed the methylation signature in 356 cytogenetically well-characterized primary hematological malignancies.
resultsDespite high expression of WT1 and AWT1 transcripts in AML-derived cell lines, we observe robust hypermethylation of the AWT1 promoter and an epigenetic switch from a permissive to repressive chromatin structure between normal cells and AML cell lines. Subsequent methylation analysis in our primary leukemia and lymphoma cohort revealed that the epigenetic signature identified in cell lines is specific to myeloid-lineage malignancies, irrespective of underlying mutational status or translocation. In addition to being a highly specific marker for AML diagnosis (positive predictive value 100%; sensitivity 86.1%; negative predictive value 89.4%), we show that AWT1 hypermethylation also discriminates patients that relapse from those achieving complete remission after hematopoietic stem cell transplantation, with similar efficiency to WT1 expression profiling.
conclusionsWe describe a methylation signature of the AWT1 promoter CpG island that is a promising marker for classifying myeloid-derived leukemias. In addition AWT1 hypermethylation is ideally suited to monitor the recurrence of disease during remission in patients undergoing allogeneic stem cell transfer.
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