ArticleBlood2015
Depletion of the chromatin remodeler CHD4 sensitizes AML blasts to genotoxic agents and reduces tumor formation.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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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.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Role of CHD4 in tumor progression, DNA damage response and treatment resistance (Review).Oncology reports · 2026Review
- The NuRD chromatin remodeling complex contributes to repairing exogenous double-strand breaks in the Caenorhabditis elegans germline.Genetics · 2026Article
- The role of epigenetic modifications in hematological cancers.Frontiers in oncology · 2026Review
- NuRD chromatin remodeling is required to repair exogenous DSBs in thebioRxiv : the preprint server for biology · 2025Article
- Epigenetic regulation of MED12: a key contributor to the leukemic chromatin landscape and transcriptional dysregulation.Epigenetics & chromatin · 2025Article
- Review
- Chromatin remodellers as therapeutic targets.Nature reviews. Drug discovery · 2024Review
- CHD4 acts as a prognostic factor and drives radioresistance in HPV negative HNSCC.Scientific reports · 2024Article
- Analysis of the complex between MBD2 and the histone deacetylase core of NuRD reveals key interactions critical for gene silencing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Identification of significant gene expression changes in multiple perturbation experiments using knockoffs.Briefings in bioinformatics · 2023Article
- Article
- The pyroptosis-related gene signature predicts prognosis and reveals characterization of the tumor immune microenvironment in acute myeloid leukemia.Frontiers in pharmacology · 2022Article
- Epigenetic modifications in acute myeloid leukemia: The emerging role of circular RNAs (Review).International journal of oncology · 2021Review
- Sentinels of chromatin: chromodomain helicase DNA-binding proteins in development and disease.Genes & development · 2021Review
- Autophagy-Dependent Sensitization of Triple-Negative Breast Cancer Models to Topoisomerase II Poisons by Inhibition of the Nucleosome Remodeling Factor.Molecular cancer research : MCR · 2021Article
- Article
- Inhibitors of Chemoresistance Pathways in Combination with Ara-C to Overcome Multidrug Resistance in AML. A Mini Review.International journal of molecular sciences · 2021Review
- CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells.International journal of molecular sciences · 2021Article
- CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer.International journal of biological sciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATPase that alters the phasing of nucleosomes on DNA and has recently been implicated in DNA double-stranded break (DSB) repair. Here, we show that depletion of CHD4 in acute myeloid leukemia (AML) blasts induces a global relaxation of chromatin that renders cells more susceptible to DSB formation, while concurrently impeding their repair. Furthermore, CHD4 depletion renders AML blasts more sensitive both in vitro and in vivo to genotoxic agents used in clinical therapy: daunorubicin (DNR) and cytarabine (ara-C). Sensitization to DNR and ara-C is mediated in part by activation of the ataxia-telangiectasia mutated pathway, which is preliminarily activated by a Tip60-dependent mechanism in response to chromatin relaxation and further activated by genotoxic agent-induced DSBs. This sensitization preferentially affects AML cells, as CHD4 depletion in normal CD34(+) hematopoietic progenitors does not increase their susceptibility to DNR or ara-C. Unexpectedly, we found that CHD4 is necessary for maintaining the tumor-forming behavior of AML cells, as CHD4 depletion severely restricted the ability of AML cells to form xenografts in mice and colonies in soft agar. Taken together, these results provide evidence for CHD4 as a novel therapeutic target whose inhibition has the potential to enhance the effectiveness of genotoxic agents used in AML therapy.
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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.