ArticleNature medicine2017
Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 143 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
143 citing papers in PubMed, 264 citations in OpenAlex.
- Exploiting an epigenetic resistance mechanism to PI3-kinase inhibition in leukemic stem cells.Leukemia · 2026Article
- Targeting HSP90 in cancer: advances in the development of inhibitors, mechanisms of action, and therapeutic applications.Molecular cancer · 2026Review
- Distal enhancer RNAs regulate alternative promoter usage of MYB and drug resistance in human leukemia cells.Leukemia · 2026Article
- Reduced PRC2 function causes asparaginase resistance in T-ALL by decreasing WNT pathway activity.Blood advances · 2026Article
- Histone modifications in biological age determination: mechanisms, biomarkers, and therapeutic perspectives.GeroScience · 2026Review
- Drug-tolerant persister cells: the deadly survivors in hematological malignancies.Frontiers in pharmacology · 2026Review
- Myeloid sarcoma shows a high frequency of mutations activating the MAPK/ERK pathway and association with clonal hematopoiesis.The journal of pathology. Clinical research · 2025Article
- Cathepsin D promotes acute myeloid leukemia progression through stabilization of the anti-apoptotic proteins.Cell death & disease · 2025Article
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Genome-wide CRISPR/Cas9 screening identifies PTGR2 as a potential therapeutic target for sunitinib resistance in clear cell renal cell carcinoma.Scientific reports · 2025Article
- Epigenetic dysregulation in acute myeloid leukemia.Seminars in hematology · 2025Review
- Multiplex gene editing models of del(7q) reveal combinedBlood neoplasia · 2025Article
- GMP-like and MLP-like Subpopulations of Hematopoietic Stem and Progenitor Cells Harboring MutatedInternational journal of molecular sciences · 2025Article
- From Chemotherapy to Targeted Therapy: Unraveling Resistance in Acute Myeloid Leukemia Through Genetic and Non-Genetic Insights.International journal of molecular sciences · 2025Review
- Review
- Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance.Functional & integrative genomics · 2025Review
- Targeting chromatin modifying complexes in acute myeloid leukemia.Stem cells translational medicine · 2025Review
- Article
- HSP90AA1 is an unfavorable prognostic factor for hepatocellular carcinoma and contributes to tumorigenesis and chemotherapy resistance.Translational oncology · 2024Article
- HNCDrugResDb: a platform for deciphering drug resistance in head and neck cancers.Scientific reports · 2024Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
28 authors at 10 institutions in 4 countries.
Funding
Abstract
In acute myeloid leukemia (AML), therapy resistance frequently occurs, leading to high mortality among patients. However, the mechanisms that render leukemic cells drug resistant remain largely undefined. Here, we identified loss of the histone methyltransferase EZH2 and subsequent reduction of histone H3K27 trimethylation as a novel pathway of acquired resistance to tyrosine kinase inhibitors (TKIs) and cytotoxic drugs in AML. Low EZH2 protein levels correlated with poor prognosis in AML patients. Suppression of EZH2 protein expression induced chemoresistance of AML cell lines and primary cells in vitro and in vivo. Low EZH2 levels resulted in derepression of HOX genes, and knockdown of HOXB7 and HOXA9 in the resistant cells was sufficient to improve sensitivity to TKIs and cytotoxic drugs. The endogenous loss of EZH2 expression in resistant cells and primary blasts from a subset of relapsed AML patients resulted from enhanced CDK1-dependent phosphorylation of EZH2 at Thr487. This interaction was stabilized by heat shock protein 90 (HSP90) and followed by proteasomal degradation of EZH2 in drug-resistant cells. Accordingly, inhibitors of HSP90, CDK1 and the proteasome prevented EZH2 degradation, decreased HOX gene expression and restored drug sensitivity. Finally, patients with reduced EZH2 levels at progression to standard therapy responded to the combination of bortezomib and cytarabine, concomitant with the re-establishment of EZH2 expression and blast clearance. These data suggest restoration of EZH2 protein as a viable approach to overcome treatment resistance in this AML patient population.
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.