ArticleNature communications2019
Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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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
112 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review of progress toward unlocking the power of epigenetics in breast cancer: latest updates and perspectives.Frontiers in pharmacology · 2025Pooled it
- A Phase I/II Open-Label Study of Molibresib for the Treatment of Relapsed/Refractory Hematologic Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- Review
- Clonal memory of cell division in humans diverges between healthy haematopoiesis and acute myeloid leukaemia.Nature communications · 2026Article
- Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia.Science translational medicine · 2026Article
- Rapid Transcription Dynamics Confers Cytarabine Resistance in Acute Myeloid Leukemia.Blood cancer discovery · 2026Article
- Dynamic, anthracycline-induced chromatin alterations enable ALDH1 expression as a mechanism of inducible leukemia resistance development.Blood research · 2026Article
- scTumorDrug: predicting cell-type-specific drug responses for heterogeneous tumors.Briefings in bioinformatics · 2026Article
- In vivo CRISPR screening identifies SAGA complex members as key regulators of hematopoiesis.Nature communications · 2026Article
- Therapeutic targeting of chromatin alterations in leukemia and solid tumors.International journal of cancer · 2026Review
- Drug-tolerant persister cells: the deadly survivors in hematological malignancies.Frontiers in pharmacology · 2026Review
- CellDuality: Unlocking Biological Reasoning in LLMs with Self-Supervised RLVR.... International Conference on Learning Representations · 2026Article
- Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026Review
- Progenitor cells, microglia, and non-coding RNAs: Orchestrators of glioblastoma pathogenesis and therapeutic resistance.Non-coding RNA research · 2025Review
- Characterization of Drug-Tolerant Persister Cells in Triple-Negative Breast Cancer Identifies a Shared Persistence Program across Treatments and Patients.Cancer research · 2025Article
- SOX9 drives a stem-like transcriptional state and platinum resistance in high-grade serous ovarian cancer.The Journal of clinical investigation · 2025Article
- Gene regulatory complexes: their role and regulation across normal and malignant hematopoiesis.Experimental hematology · 2025Review
- Integration of multi-omics approaches in exploring intra-tumoral heterogeneity.Cancer cell international · 2025Review
- Enhancer RNA-mediated transcriptional regulatory programs reveal the malignant progression of glioma.Science advances · 2025Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
36 authors.
Funding
Abstract
Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it is unknown whether stable non-genetic resistance can be overcome. Using single cell RNA-sequencing of paired drug naïve and resistant AML patient samples and cellular barcoding in a unique mouse model of non-genetic resistance, here we demonstrate that transcriptional plasticity drives stable epigenetic resistance. With a CRISPR-Cas9 screen we identify regulators of enhancer function as important modulators of the resistant cell state. We show that inhibition of Lsd1 (Kdm1a) is able to overcome stable epigenetic resistance by facilitating the binding of the pioneer factor, Pu.1 and cofactor, Irf8, to nucleate new enhancers that regulate the expression of key survival genes. This enhancer switching results in the re-distribution of transcriptional co-activators, including Brd4, and provides the opportunity to disable their activity and overcome epigenetic resistance. Together these findings highlight key principles to help counteract non-genetic drug resistance.
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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.