ArticleScientific reports2021
Loss-of-function mutations in the histone methyltransferase EZH2 promote chemotherapy resistance in AML.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- The Mutational Landscape of Acute Myeloid Leukemia and Its Impact.International journal of molecular sciences · 2026Review
- Distal enhancer RNAs regulate alternative promoter usage of MYB and drug resistance in human leukemia cells.Leukemia · 2026Article
- The role of epigenetic modifications in hematological cancers.Frontiers in oncology · 2026Review
- Integrated analysis of post-transcriptional regulations reveals insights into acute myeloid leukemia.Communications biology · 2025Article
- Analysis and Interpretation of Somatic NMD-Escaping Variants in Oncogenes and Dual-Function Genes across Adult and Pediatric Cancer Cohorts.medRxiv : the preprint server for health sciences · 2025Article
- The role of ASXL1, SRSF2, and EZH2 mutations in chromatin dysregulation of myelodysplastic neoplasia and acute myeloid leukemia.Leukemia · 2025Review
- 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
- Gene regulatory complexes: their role and regulation across normal and malignant hematopoiesis.Experimental hematology · 2025Review
- The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations.Clinical and experimental medicine · 2025Review
- Transcriptomic characterisation of acute myeloid leukemia cell lines bearing the same t(9;11) driver mutation reveals different molecular signatures.BMC genomics · 2025Article
- Hotspot gene mutations and treatment response in myelodysplastic syndromes (MDS): predictive biomarkers and targeted strategies.Frontiers in medicine · 2025Review
- Optical genome mapping identifies hidden structural variation in acute myeloid leukemia: Two case reports.Hematology, transfusion and cell therapy · 2024Article
- Epigenetic therapies targeting histone lysine methylation: complex mechanisms and clinical challenges.The Journal of clinical investigation · 2024Review
- Article
- Review
- Integrative Multi-Omics Analysis of Oncogenic EZH2 Mutants: From Epigenetic Reprogramming to Molecular Signatures.International journal of molecular sciences · 2023Article
- Review
- Comprehensive chromatin proteomics resolves functional phases of pluripotency and identifies changes in regulatory components.Nucleic acids research · 2023Article
- Heat-Shock Proteins in Leukemia and Lymphoma: Multitargets for Innovative Therapeutic Approaches.Cancers · 2023Review
- Polycomb Repressive Complex 2 in Oncology.Cancer treatment and research · 2023Article
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
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Abstract
Chemotherapy resistance is the main impediment in the treatment of acute myeloid leukaemia (AML). Despite rapid advances, the various mechanisms inducing resistance development remain to be defined in detail. Here we report that loss-of-function mutations (LOF) in the histone methyltransferase EZH2 have the potential to confer resistance against the chemotherapeutic agent cytarabine. We identify seven distinct EZH2 mutations leading to loss of H3K27 trimethylation via multiple mechanisms. Analysis of matched diagnosis and relapse samples reveal a heterogenous regulation of EZH2 and a loss of EZH2 in 50% of patients. We confirm that loss of EZH2 induces resistance against cytarabine in the cell lines HEK293T and K562 as well as in a patient-derived xenograft model. Proteomics and transcriptomics analysis reveal that resistance is conferred by upregulation of multiple direct and indirect EZH2 target genes that are involved in apoptosis evasion, augmentation of proliferation and alteration of transmembrane transporter function. Our data indicate that loss of EZH2 results in upregulation of its target genes, providing the cell with a selective growth advantage, which mediates chemotherapy resistance.
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