ArticleLeukemia2021
Identification of therapeutic targets of the hijacked super-enhancer complex in EVI1-rearranged leukemia.
Article in Leukemia, 2021. 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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The trial behind it
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Super-Enhancer-Driven SOX4/SMAD3 Mediate Membrane Remodeling by Regulating Phospholipid Metabolism to Accelerate Leukemia Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML.Leukemia · 2026Article
- USP20, a Super-enhancer Regulated Gene, Promotes Acute Myeloid Leukemia Progression through CTNNB1 Deubiquitination.International journal of biological sciences · 2026Article
- The oncogenic role of ecotropic viral integration site 1 in hematological malignancies: mechanisms of activation and leukemogenesis.Frontiers in immunology · 2026Review
- Review
- Significance of Somatic Mutation Profiling in CML Beyond BCR-ABL: A Retrospective Study of the Indian Population.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2025Article
- Proteomics appending a complementary dimension to precision oncotherapy.Computational and structural biotechnology journal · 2024Review
- Super-enhancer omics in stem cell.Molecular cancer · 2024Review
- Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML.Nature communications · 2024Article
- Super-Enhancers and Their Parts: From Prediction Efforts to Pathognomonic Status.International journal of molecular sciences · 2024Review
- Genome-wide binding analysis unveils critical implication of B-Myb-mediated transactivation in cancers.International journal of biological sciences · 2024Article
- TET2 lesions enhance the aggressiveness of CEBPA-mutant acute myeloid leukemia by rebalancing GATA2 expression.Nature communications · 2023Article
- EVI1-mediated Programming of Normal and Malignant Hematopoiesis.HemaSphere · 2023Review
- High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma.Journal of ovarian research · 2023Article
- Review
- 3q26.2/Cancers · 2023Article
- Super enhancers: Pathogenic roles and potential therapeutic targets for acute myeloid leukemia (AML).Genes & diseases · 2022Review
- Phase I Clinical Trial of DNA Methyltransferase Inhibitor Decitabine and PARP Inhibitor Talazoparib Combination Therapy in Relapsed/Refractory Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- GATA2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program.Blood advances · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Deregulation of the EVI1 proto-oncogene by the GATA2 distal hematopoietic enhancer (G2DHE) is a key event in high-risk acute myeloid leukemia carrying 3q21q26 aberrations (3q-AML). Upon chromosomal rearrangement, G2DHE acquires characteristics of a super-enhancer and causes overexpression of EVI1 at 3q26.2. However, the transcription factor (TF) complex of G2DHE remains poorly characterized. The aim of this study was to unravel key components of G2DHE-bound TFs involved in the deregulation of EVI1. We have identified several CEBPA and RUNX1 binding sites to be enriched and critical for G2DHE function in 3q-AML cells. Using ChIP-SICAP (ChIP followed by selective isolation of chromatin-associated proteins), a panel of chromatin interactors of RUNX1 and CEBPA were detected in 3q-AML, including PARP1 and IKZF1. PARP1 inhibition (PARPi) caused a reduction of EVI1 expression and a decrease in EVI1-G2DHE interaction frequency, highlighting the involvement of PARP1 in oncogenic super-enhancer formation. Furthermore, 3q-AML cells were highly sensitive to PARPi and displayed morphological changes with higher rates of differentiation and apoptosis as well as depletion of CD34 + cells. In summary, integrative analysis of the 3q-AML super-enhancer complex identified CEBPA and RUNX1 associated proteins and nominated PARP1 as a potential new therapeutic target in EVI1 + 3q-AML.
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Registered trials
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