ArticleCancer discovery2022
Integrated Multiomic Profiling Identifies the Epigenetic Regulator PRC2 as a Therapeutic Target to Counteract Leukemia Immune Escape and Relapse.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 50 citations in OpenAlex.
- Review
- Therapy induced senescence promotes immunogenicity in acute myeloid Leukemia through reduced EZH2 activity.Nature communications · 2026Article
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- Optimal donor selection for transplant to reduce GVHD risk and augment graft-versus-malignancy efficacy.Current opinion in immunology · 2026Review
- Mutational landscape changes of AML in patients relapsing after allogeneic hematopoietic cell transplantation.Bone marrow transplantation · 2026Article
- GFI1 enhances MHC-I expression in tumor cells and augments tumor responsiveness to PD-1/PD-L1 inhibitors.Cancer immunology, immunotherapy : CII · 2026Article
- MHC class I on target cells regulates CD4Nature immunology · 2026Article
- Genomic and Immune Correlates of EZH2 Expression and Activity in Olfactory Neuroblastoma.Head & neck · 2026Article
- Novel approaches for separating graft-versus-leukemia effects from graft-versus-host disease.Frontiers in oncology · 2026Review
- In situ extended immune activation instantly after tumor resection by oncolytic virus controls postoperative tumor recurrence.Cell reports. Medicine · 2025Article
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Article
- Immune Escape of Acute Myeloid Leukemia after Transplantation.Blood cancer discovery · 2025Review
- Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance.Functional & integrative genomics · 2025Review
- Cancer stem cells and niches: challenges in immunotherapy resistance.Molecular cancer · 2025Review
- Advances in the application of patient-derived xenograft models in acute leukemia resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Biology of post-transplant relapse: actionable features.Hematology. American Society of Hematology. Education Program · 2024Review
- Bi-functional CpG-STAT3 decoy oligonucleotide triggers multilineage differentiation of acute myeloid leukemia in mice.Molecular therapy. Nucleic acids · 2024Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune escape represents a major driver of acute myeloid leukemia (AML) reemergence after allogeneic hematopoietic cell transplantation (allo-HCT), with up to 40% of relapses prompted by nongenomic loss of HLA class II expression in leukemia cells. By integrative analysis of gene expression, DNA methylation, and chromatin accessibility in paired diagnosis/relapse primary samples and in the respective patient-derived xenografts (PDX), we identify the polycomb repressive complex 2 (PRC2) as a key epigenetic driver of this immune escape modality. We report that loss of expression of HLA class II molecules is accompanied by a PRC2-dependent reduction in chromatin accessibility. Pharmacologic inhibition of PRC2 subunits rescues HLA class II expression in AML relapses in vitro and in vivo, with consequent recovery of leukemia recognition by CD4+ T cells. Our results uncover a novel link between epigenetics and leukemia immune escape, which may rapidly translate into innovative strategies to cure or prevent AML posttransplantation relapse. SIGNIFICANCE: Loss of HLA class II expression represents a frequent mechanism of leukemia posttransplantation relapse. Here we identify PRC2 as the main epigenetic driver of this immune escape modality and show that its chemical inhibition can reinstate a proficient graft-versus-leukemia effect, providing an innovative rationale for personalized epigenetic immunotherapies. See related commentary by Köhler and Zeiser, p. 1410. This article is highlighted in the In This Issue feature, p. 1397.
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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.