ArticleCancer discovery2016
Epigenetic Reprogramming Sensitizes CML Stem Cells to Combined EZH2 and Tyrosine Kinase Inhibition.
Article in Cancer discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 132 citations in OpenAlex.
- Treatment-Free Remission in Chronic Myeloid Leukemia: Toward Precision and Personalized Approaches to Functional Cure.Cancer science · 2026Review
- Enhancer of Zeste Homolog 2 (EZH2): From Glioblastoma Biology to Potential Epigenetic Therapy.International journal of molecular sciences · 2026Review
- TheHematology reports · 2026Article
- Intrinsic cellular resistance to BCR::ABL1 inhibitors.Haematologica · 2026Review
- Understanding drug resistance in chronic myeloid leukemia through the lens of leukemic stem cell states: insights from single-cell analyses.Haematologica · 2026Review
- The disulfonic acid ANDS disrupts ANP32B-p53 interaction to suppress chronic myeloid leukemia.Nature communications · 2026Article
- Epigenetic alterations in Myeloid Malignancies.Advances in experimental medicine and biology · 2026Review
- The interplay of DNA damage, epigenetics and tumour heterogeneity in driving cancer cell fitness.Nature communications · 2025Review
- Treatment-Free Remission in Chronic Myeloid Leukemia: Revisiting the "W" Questions.European journal of haematology · 2025Review
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- EZH2 modulates mRNA splicing and exerts part of its oncogenic function through repression of splicing factors in CML.Leukemia · 2025Article
- Review
- LncRNAiScience · 2024Article
- Insights into existing and futuristic treatment approach for chronic myeloid leukaemia.The Indian journal of medical research · 2024Review
- Harnessing the potential of reverse-phase protein array technology: Advancing precision oncology strategies.Cancer science · 2024Review
- Inhibition of mitochondrial folate metabolism drives differentiation through mTORC1 mediated purine sensing.Nature communications · 2024Article
- Activating p53 abolishes self-renewal of quiescent leukaemic stem cells in residual CML disease.Nature communications · 2024Article
- Arginine dependency is a therapeutically exploitable vulnerability in chronic myeloid leukaemic stem cells.EMBO reports · 2023Article
- Genetic Landscape of Chronic Myeloid Leukemia and a Novel Targeted Drug for Overcoming Resistance.International journal of molecular sciences · 2023Review
- Pyruvate anaplerosis is a targetable vulnerability in persistent leukaemic stem cells.Nature communications · 2023Article
17 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
17 authors at 2 institutions in 1 country.
Funding
Abstract
A major obstacle to curing chronic myeloid leukemia (CML) is residual disease maintained by tyrosine kinase inhibitor (TKI)-persistent leukemic stem cells (LSC). These are BCR-ABL1 kinase independent, refractory to apoptosis, and serve as a reservoir to drive relapse or TKI resistance. We demonstrate that Polycomb Repressive Complex 2 is misregulated in chronic phase CML LSCs. This is associated with extensive reprogramming of H3K27me3 targets in LSCs, thus sensitizing them to apoptosis upon treatment with an EZH2-specific inhibitor (EZH2i). EZH2i does not impair normal hematopoietic stem cell survival. Strikingly, treatment of primary CML cells with either EZH2i or TKI alone caused significant upregulation of H3K27me3 targets, and combined treatment further potentiated these effects and resulted in significant loss of LSCs compared to TKI alone, in vitro, and in long-term bone marrow murine xenografts. Our findings point to a promising epigenetic-based therapeutic strategy to more effectively target LSCs in patients with CML receiving TKIs. SIGNIFICANCE: In CML, TKI-persistent LSCs remain an obstacle to cure, and approaches to eradicate them remain a significant unmet clinical need. We demonstrate that EZH2 and H3K27me3 reprogramming is important for LSC survival, but renders LSCs sensitive to the combined effects of EZH2i and TKI. This represents a novel approach to more effectively target LSCs in patients receiving TKI treatment. Cancer Discov; 6(11); 1248-57. ©2016 AACR.See related article by Xie et al., p. 1237This article is highlighted in the In This Issue feature, p. 1197.
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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.