ArticleNature communications2024
Epigenetic regulation of CD38/CD48 by KDM6A mediates NK cell response in multiple myeloma.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Inflammatory bone marrow microenvironment impairs the therapeutic effect of daratumumab-lenalidomide in multiple myeloma.Biomarker research · 2026Article
- CRISPR application in hematological disorders: from bench to bedside.Blood advances · 2026Review
- Shared diagnostic biomarkers in metabolic syndrome and coronary artery disease identified by integrated bioinformatics and machine learning.Endocrine connections · 2026Article
- Extending structural surfaceomics to identify aberrant conformations of tumor surface proteins as potential immunotherapy targets.bioRxiv : the preprint server for biology · 2026Article
- Ablation of CD38 in multiple myeloma cells leads to an aggressive phenotype in a mouse xenograft model.Blood advances · 2026Article
- Epigenetic reprogramming in multiple myeloma-Challenges and opportunities.International journal of cancer · 2026Review
- Regulating the regulators via targeting CD38 in the tumor microenvironment.Frontiers in immunology · 2026Review
- Ferroptosis in multiple myeloma: molecular mechanisms and therapeutic opportunities.Frontiers in oncology · 2026Review
- Differentiated Thyroid Cancer Is Associated With Sex-specific Immune Response.Journal of the Endocrine Society · 2026Article
- Single-cell transcriptomics and spatial validation reveal dysfunction of keratinocytes and NK cells driving acne development.Scientific reports · 2025Article
- Targeting Wnt/β-catenin signaling enhances the efficacy of anti-CD38 immunotherapy in multiple myeloma.Neoplasia (New York, N.Y.) · 2025Article
- Lysine demethylases 6 A and 6B as epigenetic regulators in therapeutic resistance of cancer.Clinical epigenetics · 2025Review
- Article
- Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential.Biomarker research · 2025Review
- Multiple myeloma with 1q gain/amplification exhibits reduced CD38 expression via interleukin-6 receptor overexpression.British journal of haematology · 2025Article
- KDM6A Deficiency Induces Myeloid Bias and Promotes CMML-Like Disease Through JAK/STAT3 Activation by Repressing SOCS3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SLAMF receptors: key regulators of tumor progression and emerging targets for cancer immunotherapy.Molecular cancer · 2025Review
- The de novo DNA methyltransferase 3B is a novel epigenetic regulator of MYC in multiple myeloma, representing a promising therapeutic target to counter relapse.Journal of experimental & clinical cancer research : CR · 2025Article
- Research trends and highlights in PD-1/PD-L1 inhibitor immunotherapy in lung cancer: a bibliometric analysis.Discover oncology · 2025Article
- Engineered mesenchymal stromal cells with bispecific polyvalent peptides suppress excessive neutrophil infiltration and boost therapy.Science advances · 2025Article
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Anti-CD38 monoclonal antibodies like Daratumumab (Dara) are effective in multiple myeloma (MM); however, drug resistance ultimately occurs and the mechanisms behind this are poorly understood. Here, we identify, via two in vitro genome-wide CRISPR screens probing Daratumumab resistance, KDM6A as an important regulator of sensitivity to Daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Loss of KDM6A leads to increased levels of H3K27me3 on the promoter of CD38, resulting in a marked downregulation in CD38 expression, which may cause resistance to Daratumumab-mediated ADCC. Re-introducing CD38 does not reverse Daratumumab-mediated ADCC fully, which suggests that additional KDM6A targets, including CD48 which is also downregulated upon KDM6A loss, contribute to Daratumumab-mediated ADCC. Inhibition of H3K27me3 with an EZH2 inhibitor resulted in CD38 and CD48 upregulation and restored sensitivity to Daratumumab. These findings suggest KDM6A loss as a mechanism of Daratumumab resistance and lay down the proof of principle for the therapeutic application of EZH2 inhibitors, one of which is already FDA-approved, in improving MM responsiveness to Daratumumab.
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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.