ArticleOncotarget2016
The histone methyltransferase EZH2 as a novel prosurvival factor in clinically aggressive chronic lymphocytic leukemia.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- The Chronic Lymphocytic Leukemia Epigenome: A Powerful and Stable Framework for Understanding Biological and Clinical Heterogeneity.Hematology/oncology clinics of North America · 2025Review
- Unraveling the Epigenetic Landscape of Mature B Cell Neoplasia: Mechanisms, Biomarkers, and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Multiple omics levels of chronic lymphocytic leukemia.Cell death discovery · 2024Review
- Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.Signal transduction and targeted therapy · 2023Review
- In silico investigations identified Butyl Xanalterate to competently target CK2α (CSNK2A1) for therapy of chronic lymphocytic leukemia.Scientific reports · 2022Article
- Mechanisms of Polycomb group protein function in cancer.Cell research · 2022Review
- RPPA-based proteomics recognizes distinct epigenetic signatures in chronic lymphocytic leukemia with clinical consequences.Leukemia · 2022Article
- EZH2 expression is associated with inferior overall survival in mantle cell lymphoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Article
- Control of PD-L1 expression in CLL-cells by stromal triggering of the Notch-c-Myc-EZH2 oncogenic signaling axis.Journal for immunotherapy of cancer · 2021Article
- Stem cell factor is implicated in microenvironmental interactions and cellular dynamics of chronic lymphocytic leukemia.Haematologica · 2021Article
- Chromatin remodeling by the histone methyltransferase EZH2 drives lung pre-malignancy and is a target for cancer prevention.Clinical epigenetics · 2021Article
- Aspartic Aminopeptidase Is a Novel Biomarker of Aggressive Chronic Lymphocytic Leukemia.Cancers · 2020Article
- DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy.Clinical epigenetics · 2019Article
- EZH2 upregulates the PI3K/AKT pathway through IGF1R and MYC in clinically aggressive chronic lymphocytic leukaemia.Epigenetics · 2019Article
- Inhibition of EZH2 and immune signaling exerts synergistic antitumor effects in chronic lymphocytic leukemia.Blood advances · 2019Article
- Polycomb Repressor Complex 2 in Genomic Instability and Cancer.International journal of molecular sciences · 2017Review
- Article
- Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control.Blood cancer journal · 2017Article
- Aberrant histone modification in CD19OncoTargets and therapy · 2017Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The histone methyltransferase EZH2 induces gene repression through trimethylation of histone H3 at lysine 27 (H3K27me3). EZH2 overexpression has been reported in many types of cancer and associated with poor prognosis. Here we investigated the expression and functionality of EZH2 in chronic lymphocytic leukemia (CLL). Aggressive cases with unmutated IGHV genes (U-CLL) displayed significantly higher EZH2 expression compared to indolent CLL cases with mutated IGHV genes (M-CLL); furthermore, in U-CLL EZH2 expression was upregulated with disease progression. Within U-CLL, EZH2high cases harbored significantly fewer (p = 0.033) TP53 gene abnormalities compared to EZH2low cases. EZH2high cases displayed high H3K27me3 levels and increased viability suggesting that EZH2 is functional and likely confers a survival advantage to CLL cells. This argument was further supported by siRNA-mediated downmodulation of EZH2 which resulted in increased apoptosis. Notably, at the intraclonal level, cell proliferation was significantly associated with EZH2 expression. Treatment of primary CLL cells with EZH2 inhibitors induced downregulation of H3K27me3 levels leading to increased cell apoptosis. In conclusion, EZH2 is overexpressed in adverse-prognosis CLL and associated with increased cell survival and proliferation. Pharmacologic inhibition of EZH2 catalytic activity promotes apoptosis, highlighting EZH2 as a novel potential therapeutic target for specific subgroups of patients with CLL.
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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.