ArticleBlood2024
Acute myeloid leukemias with UBTF tandem duplications are sensitive to menin inhibitors.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 50 citations in OpenAlex.
- Menin Inhibition With Revumenib forJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Menin inhibition in pediatric UBTF-TD myelodysplastic syndrome: molecular rationale and clinical observation.Molecular and cellular pediatrics · 2026Article
- Targeting Exportin-1 in Cancer: From Nuclear Export to Oncogenic Transcriptional Hubs.JMA journal · 2026Review
- Menin Inhibitors in Acute Myeloid Leukemia: Clinical Integration, Resistance, and the Path Beyond Monotherapy.Cancers · 2026Review
- A New Paradigm for Pediatric AML: Improving the Pipeline for Treatments Targeting Cytogenetic and Molecular Alterations.Cancers · 2026Review
- Co-option of lineage plasticity as a hallmark of multipotent acute leukemias.Blood neoplasia · 2026Review
- Menin inhibitors as a treatment for acute leukemia: from bench to the clinic.Blood neoplasia · 2026Review
- The new era of AML therapy: current standards and emerging targets.International journal of clinical oncology · 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
- Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.International journal of cancer · 2026Review
- Tandem Duplications in UBTF Create XPO1-Dependent Nuclear Export Signals that Reveal a Leukemic Therapeutic Dependency.Blood cancer discovery · 2026Article
- Genetic landscape of pediatric acute myeloid leukemia in Taiwan.Scientific reports · 2026Article
- Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy.NPJ precision oncology · 2025Review
- Rapid epigenomic classification of acute leukemia.Nature genetics · 2025Article
- Precision oncology to overcome resistance in R/R AML in children and adults requires combinations of cytotoxic, targeted, and immunological treatments.Journal of internal medicine · 2025Review
- Novel classification system and high-risk categories of pediatric acute myeloid leukemia.Haematologica · 2025Review
- Epigenetic dysregulation in acute myeloid leukemia.Seminars in hematology · 2025Review
- Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia.Haematologica · 2025Article
- Integrated Computational and Functional Screening Identifies G9a Inhibitors for SETD2-mutant Leukemia.Genomics, proteomics & bioinformatics · 2025Article
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28 authors at 2 institutions in 3 countries.
Funding
Abstract
abstractUBTF tandem duplications (UBTF-TDs) have recently emerged as a recurrent alteration in pediatric and adult acute myeloid leukemia (AML). UBTF-TD leukemias are characterized by a poor response to conventional chemotherapy and a transcriptional signature that mirrors NUP98-rearranged and NPM1-mutant AMLs, including HOX-gene dysregulation. However, the mechanism by which UBTF-TD drives leukemogenesis remains unknown. In this study, we investigated the genomic occupancy of UBTF-TD in transformed cord blood CD34+ cells and patient-derived xenograft models. We found that UBTF-TD protein maintained genomic occupancy at ribosomal DNA loci while also occupying genomic targets commonly dysregulated in UBTF-TD myeloid malignancies, such as the HOXA/HOXB gene clusters and MEIS1. These data suggest that UBTF-TD is a gain-of-function alteration that results in mislocalization to genomic loci dysregulated in UBTF-TD leukemias. UBTF-TD also co-occupies key genomic loci with KMT2A and menin, which are known to be key partners involved in HOX-dysregulated leukemias. Using a protein degradation system, we showed that stemness, proliferation, and transcriptional signatures are dependent on sustained UBTF-TD localization to chromatin. Finally, we demonstrate that primary cells from UBTF-TD leukemias are sensitive to the menin inhibitor SNDX-5613, resulting in markedly reduced in vitro and in vivo tumor growth, myeloid differentiation, and abrogation of the UBTF-TD leukemic expression signature. These findings provide a viable therapeutic strategy for patients with this high-risk AML subtype.
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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.