ArticleLeukemia2020
Loss of KDM6A confers drug resistance in acute myeloid leukemia.
Article in Leukemia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 99 citations in OpenAlex.
- Epigenetic Factor Dysregulation and Distinct Expression Signatures in Retinoblastoma: A Transcriptomic Analysis.Investigative ophthalmology & visual science · 2026Article
- PML::RARA-negative APL-mimicking AML with a novel KMT2C::CREB3L2 fusion and RARA/RXRA-mediated sensitivity to all-trans retinoic acid.Annals of hematology · 2026Article
- Papillary renal cell carcinoma, formerly known as Type 2: a single institutional study addressing histologic and molecular features.Histopathology · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Genomic profile of an IDH-wild-type glioblastoma diagnosed following TNF-α inhibitor therapy: a molecular case study.Frontiers in oncology · 2026Article
- Dissecting the role of epigenetic regulation in oral squamous cell carcinoma microenvironment: mechanisms and therapeutics.Frontiers in immunology · 2026Review
- Lysine demethylases 6 A and 6B as epigenetic regulators in therapeutic resistance of cancer.Clinical epigenetics · 2025Review
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Article
- KDM6A Deficiency Induces Myeloid Bias and Promotes CMML-Like Disease Through JAK/STAT3 Activation by Repressing SOCS3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Clonal composition of karyotypically normal AML at diagnosis is not affected by the microenvironment.Blood neoplasia · 2025Article
- Review
- Targeting chromatin modifying complexes in acute myeloid leukemia.Stem cells translational medicine · 2025Review
- Genetic abnormalities predict outcomes in patients with core binding factor acute myeloid leukemia.Annals of hematology · 2025Article
- FGFC1 overcomes Ara-C resistance in acute myeloid leukemia by inducing apoptosis and pyroptosis.Frontiers in pharmacology · 2025Article
- Editorial: Histone modifications in cancer.Frontiers in pharmacology · 2025Article
- Unveiling the molecular profile of a prostate carcinoma: implications for personalized medicine.Biology direct · 2024Article
- KDM6A-SND1 interaction maintains genomic stability by protecting the nascent DNA and contributes to cancer chemoresistance.Nucleic acids research · 2024Article
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
- Chemotherapy resistance in acute myeloid leukemia is associated with decreased anti-tumor immune response through MHC molecule and B7 family members.Discover oncology · 2024Article
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm resulting from the malignant transformation of myeloid progenitors. Despite intensive chemotherapy leading to initial treatment responses, relapse caused by intrinsic or acquired drug resistance represents a major challenge. Here, we report that histone 3 lysine 27 demethylase KDM6A (UTX) is targeted by inactivating mutations and mutation-independent regulation in relapsed AML. Analyses of matched diagnosis and relapse specimens from individuals with KDM6A mutations showed an outgrowth of the KDM6A mutated tumor population at relapse. KDM6A expression is heterogeneously regulated and relapse-specific loss of KDM6A was observed in 45.7% of CN-AML patients. KDM6A-null myeloid leukemia cells were more resistant to treatment with the chemotherapeutic agents cytarabine (AraC) and daunorubicin. Inducible re-expression of KDM6A in KDM6A-null cell lines suppressed proliferation and sensitized cells again to AraC treatment. RNA expression analysis and functional studies revealed that resistance to AraC was conferred by downregulation of the nucleoside membrane transporter ENT1 (SLC29A1) by reduced H3K27 acetylation at the ENT1 locus. Our results show that loss of KDM6A provides cells with a selective advantage during chemotherapy, which ultimately leads to the observed outgrowth of clones with KDM6A mutations or reduced KDM6A expression at relapse.
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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.