ArticleBlood2015
Mutant WT1 is associated with DNA hypermethylation of PRC2 targets in AML and responds to EZH2 inhibition.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 55 citations in OpenAlex.
- A precision medicine classification for treatment of acute myeloid leukemia in older patients.Journal of hematology & oncology · 2021Trial
- DNA Methylation Stochasticity Is Linked to Transcriptional Variability and Convergent Epigenetic Disruption across Genetic Subtypes of Acute Myeloid Leukemia.Cancer research · 2026Article
- Hypomethylation ofFrontiers in immunology · 2025Article
- Investigating the Role of HOTAIR and MALAT1 Long Noncoding RNAs and Their Relations With Bone Marrow Environment in Acute Myeloid Leukemia Subtypes: Biomarkers and Treatment Response.Advances in hematology · 2025Review
- Review
- Tumor suppressor CEBPA interacts with and inhibits DNMT3A activity.Science advances · 2022Article
- Tumor suppressor function ofHaematologica · 2022Article
- Thymoquinone Inhibits Growth of Acute Myeloid Leukemia Cells through ReversalPharmaceuticals (Basel, Switzerland) · 2021Article
- Article
- Review
- RNA-Binding Proteins in Acute Leukemias.International journal of molecular sciences · 2020Review
- The phosphatidylethanolamine biosynthesis pathway provides a new target for cancer chemotherapy.Journal of hepatology · 2020Article
- Molecular update on biology of Wilms Tumor 1 gene and its applications in acute myeloid leukemia.American journal of blood research · 2020Review
- Review
- MutatedJournal of oncology · 2019Article
- The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions.Nature medicine · 2018Article
- A CpG island methylator phenotype in acute myeloid leukemia independent of IDH mutations and associated with a favorable outcome.Leukemia · 2017Article
- Pharmacologic Targeting of Chromatin Modulators As Therapeutics of Acute Myeloid Leukemia.Frontiers in oncology · 2017Review
- Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia.Haematologica · 2016Review
- Molecular therapy for acute myeloid leukaemia.Nature reviews. Clinical oncology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Acute myeloid leukemia (AML) is associated with deregulation of DNA methylation; however, many cases do not bear mutations in known regulators of cytosine guanine dinucleotide (CpG) methylation. We found that mutations in WT1, IDH2, and CEBPA were strongly linked to DNA hypermethylation in AML using a novel integrative analysis of The Cancer Genome Atlas data based on Boolean implications, if-then rules that identify all individual CpG sites that are hypermethylated in the presence of a mutation. Introduction of mutant WT1 (WT1mut) into wild-type AML cells induced DNA hypermethylation, confirming mutant WT1 to be causally associated with DNA hypermethylation. Methylated genes in WT1mut primary patient samples were highly enriched for polycomb repressor complex 2 (PRC2) targets, implicating PRC2 dysregulation in WT1mut leukemogenesis. We found that PRC2 target genes were aberrantly repressed in WT1mut AML, and that expression of mutant WT1 in CD34(+) cord blood cells induced myeloid differentiation block. Treatment of WT1mut AML cells with short hairpin RNA or pharmacologic PRC2/enhancer of zeste homolog 2 (EZH2) inhibitors promoted myeloid differentiation, suggesting EZH2 inhibitors may be active in this AML subtype. Our results highlight a strong association between mutant WT1 and DNA hypermethylation in AML and demonstrate that Boolean implications can be used to decipher mutation-specific methylation patterns that may lead to therapeutic insights.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.