ArticleBlood2024
Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
33 citing papers in PubMed.
- Two Decades ofCancers · 2026Review
- The case for prospective MEN1 surveillance in the era of sequential menin inhibitor therapy.Leukemia · 2026Article
- Menin Inhibitors in Acute Myeloid Leukemia: Clinical Integration, Resistance, and the Path Beyond Monotherapy.Cancers · 2026Review
- Blocking SETD2 Enhances the Therapeutic Efficiency of Menin Inhibitor in MLL-Fusion Leukemia.Cancer science · 2026Article
- Menin inhibitors as a treatment for acute leukemia: from bench to the clinic.Blood neoplasia · 2026Review
- Menin Inhibition in Acute Myeloid Leukemia: Rewiring Leukemic Transcriptional Networks.International journal of molecular sciences · 2026Review
- CRISPR base editor screening identifies spectrum of MEN1 mutations impacting menin inhibitors in clinical trials.Nature communications · 2026Article
- A Perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged acute myeloid leukemia.Leukemia · 2026Article
- Current perspectives on KMT2A fusion proteins and menin inhibition in paediatric acute myeloid leukaemia.The FEBS journal · 2026Review
- Review
- Disrupting the ASH2L-DPY30 PPI in cancer: structure, function, and therapeutic opportunities in H3K4 methylation.Epigenetics & chromatin · 2026Review
- Targeted Therapy in Acute Myeloid Leukemia: Current Approaches and Novel Directions.Journal of personalized medicine · 2026Review
- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- Menin Inhibition in Acute Myeloid MLL Rearranged Leukemias: A New Target for Precision Care.Cancers · 2026Review
- Review
- Dynamic heterogeneity towards drug resistance in AML cells is primarily driven by epigenomic mechanism unveiled by multi-omics analysis.Journal of advanced research · 2026Article
- Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.International journal of cancer · 2026Review
- Clinical Integration of Menin Inhibitors in AML: Evolving Data and Therapeutic Perspectives.Oncology research · 2026Review
- Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy.NPJ precision oncology · 2025Review
- The promise of menin inhibitors: from approval to triplet regimens.Hematology. American Society of Hematology. Education Program · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
abstractMenin inhibitors that disrupt the menin-MLL interaction hold promise for treating specific acute myeloid leukemia (AML) subtypes, including those with KMT2A rearrangements (KMT2A-r), yet resistance remains a challenge. Here, through systematic chromatin-focused CRISPR screens, along with genetic, epigenetic, and pharmacologic studies in a variety of human and mouse KMT2A-r AML models, we uncovered a potential resistance mechanism independent of canonical menin-MLL targets. We show that a group of noncanonical menin targets, which are bivalently cooccupied by active menin and repressive H2AK119ub marks, are typically downregulated after menin inhibition. Loss of polycomb repressive complex 1.1 (PRC1.1) subunits, such as polycomb group ring finger 1 (PCGF1) or BCL6 corepressor (BCOR), leads to menin inhibitor resistance by epigenetic reactivation of these noncanonical targets, including MYC. Genetic and pharmacological inhibition of MYC can resensitize PRC1.1-deficient leukemia cells to menin inhibition. Moreover, we demonstrate that leukemia cells with the loss of PRC1.1 subunits exhibit reduced monocytic gene signatures and are susceptible to BCL2 inhibition, and that combinational treatment with venetoclax overcomes the resistance to menin inhibition in PRC1.1-deficient leukemia cells. These findings highlight the important roles of PRC1.1 and its regulated noncanonical menin targets in modulating the menin inhibitor response and provide potential strategies to treat leukemia with compromised PRC1.1 function.
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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.