ArticleLeukemia2019
Ikaros tumor suppressor function includes induction of active enhancers and super-enhancers along with pioneering activity.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Bibliometric Analysis of ATAC-Seq and Its Use in Cancer Biology via Nucleic Acid Detection.Frontiers in medicine · 2020Pooled it
- Manipulation of Alternative Splicing ofCells · 2026Article
- The role of LLPS of biomacromolecules in the gonads and related diseases.Frontiers in endocrinology · 2026Review
- PBK/TOPK mediates Ikaros, Aiolos and CTCF displacement from mitotic chromosomes and alters chromatin accessibility at selected C2H2-zinc finger protein binding sites.Nature communications · 2025Article
- Critical roles of IKAROS and HDAC1 in regulation of heterochromatin and tumor suppression in T-cell acute lymphoblastic leukemia.Leukemia · 2025Article
- Article
- Super-enhancers in tumors: unraveling recent advances in their role in Oncogenesis and the emergence of targeted therapies.Journal of translational medicine · 2025Review
- IKAROS: from chromatin organization to transcriptional elongation control.Cell death and differentiation · 2025Review
- Mycovirus-ContainingInternational journal of molecular sciences · 2024Article
- Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma.Blood cancer discovery · 2024Article
- IKAROS Family Transcription Factors in Lymphocyte Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Review
- Protein kinase CK2 - diverse roles in cancer cell biology and therapeutic promise.Molecular and cellular biochemistry · 2023Review
- Genetics of Immune Dysregulation and Cancer Predisposition: Two Sides of the Same Coin.Clinical and experimental immunology · 2022Review
- IKAROS and MENIN coordinate therapeutically actionable leukemogenic gene expression in MLL-r acute myeloid leukemia.Nature cancer · 2022Article
- Novel Molecular Mechanism of Lenalidomide in Myeloid Malignancies Independent of Deletion of Chromosome 5q.Cancers · 2021Review
- Altered DNA Methylation Profiles inInternational journal of molecular sciences · 2021Article
- Dual targeting of MTOR as a novel therapeutic approach for high-risk B-cell acute lymphoblastic leukemia.Leukemia · 2021Article
- A Point Mutation in IKAROS ZF1 Causes a B Cell Deficiency in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Mechanistic Basis for In Vivo Therapeutic Efficacy of CK2 Inhibitor CX-4945 in Acute Myeloid Leukemia.Cancers · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Ikaros encodes a transcription factor that functions as a tumor suppressor in T-cell acute lymphoblastic leukemia (T-ALL). The mechanisms through which Ikaros regulates gene expression and cellular proliferation in T-ALL are unknown. Re-introduction of Ikaros into Ikaros-null T-ALL cells resulted in cessation of cellular proliferation and induction of T-cell differentiation. We performed dynamic, global, epigenomic, and gene expression analyses to determine the mechanisms of Ikaros tumor suppressor activity. Our results identified novel Ikaros functions in the epigenetic regulation of gene expression: Ikaros directly regulates de novo formation and depletion of enhancers, de novo formation of active enhancers and activation of poised enhancers; Ikaros directly induces the formation of super-enhancers; and Ikaros demonstrates pioneering activity by directly regulating chromatin accessibility. Dynamic analyses demonstrate the long-lasting effects of Ikaros DNA binding on enhancer activation, de novo formation of enhancers and super-enhancers, and chromatin accessibility. Our results establish that Ikaros' tumor suppressor function occurs via global regulation of the enhancer and super-enhancer landscape and through pioneering activity. Expression analysis identified a large number of novel signaling pathways that are directly regulated by Ikaros and Ikaros-induced enhancers, and that are responsible for the cessation of proliferation and induction of T-cell differentiation in T-ALL cells.
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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.