ArticleBlood cancer journal2023
Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1.
Article in Blood cancer journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 52 citations in OpenAlex.
- Menin Inhibitors in Acute Myeloid Leukemia: Clinical Integration, Resistance, and the Path Beyond Monotherapy.Cancers · 2026Review
- Menin inhibitors as a treatment for acute leukemia: from bench to the clinic.Blood neoplasia · 2026Review
- TCA-controlled histone succinylation identifies IDH3B as a prognostic and therapeutic target in AML.Clinical epigenetics · 2026Article
- Menin Inhibition in Acute Myeloid Leukemia: Rewiring Leukemic Transcriptional Networks.International journal of molecular sciences · 2026Review
- 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
- Outcomes of relapsed or refractory acute myeloid leukemia after menin inhibition failure.Blood advances · 2026Article
- Article
- Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.International journal of cancer · 2026Review
- Menin-MLL1 complex cooperates with NF-Y to promote hepatocellular carcinoma survival.Cell reports · 2025Article
- Optical genome mapping identifies novel ENOX2::RUNX1 t(X;21)(q26.1;q22.12) rearrangement in acute myeloid leukemia-myelodysplasia related: first case report.Molecular cytogenetics · 2025Article
- Exploiting artificial intelligence in precision oncology: an updated comprehensive review.Journal of translational medicine · 2025Review
- 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
- Targeting menin in lysine methyltransferase 2A/nucleophosmin-mutated leukemia: A novel strategy from epigenetic dysregulation to clinical therapy (Review).Oncology letters · 2025Review
- KMT2A-rearranged leukemia: from mechanism to drug development.Experimental hematology · 2025Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Co-targeting menin and LSD1 dismantles oncogenic programs and restores differentiation in MLL-rearranged AML.bioRxiv : the preprint server for biology · 2025Article
- ENO1-BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism.Journal of molecular cell biology · 2025Article
- The role of multivalency in the association of the eight twenty-one protein 2 (ETO2) with the nucleosome remodeling and deacetylase (NuRD) complex.Nucleic acids research · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A protein domain-focused CRISPR-Cas9 screen in MLL1-r AML cells identified targetable co-dependencies with MI treatment, including BRD4, EP300, MOZ and KDM1A. Consistent with this, in vitro co-treatment with MI and BET, MOZ, LSD1 or CBP/p300 inhibitor induced synergistic loss of viability of AML cells with MLL1-r or mtNPM1. Co-treatment with MI and BET or CBP/p300 inhibitor also exerted significantly superior in vivo efficacy in xenograft models of AML with MLL1-r. These findings highlight novel, MI-based combinations that could prevent escape of AML stem/progenitor cells following MI monotherapy, which is responsible for therapy-refractory AML 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.