ArticleBlood2022
The menin-MLL1 interaction is a molecular dependency in NUP98-rearranged AML.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 134 citations in OpenAlex.
- A phase 1/2 study of DS-1594 menin inhibitor in relapsed/refractory acute leukemias.Journal of hematology & oncology · 2025Trial
- Menin Inhibition With Revumenib forJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Clinical impact of minimal residual disease in blood and bone marrow of children with acute myeloid leukemia.Blood advances · 2023Trial
- Targeting the Epigenetic-Immune Axis in Acute Myeloid Leukemia: Current Advances and Future Directions.Current oncology reports · 2026Review
- Nucleoporins in Cancer: Functional Roles and Therapeutic Opportunities.Cancer discovery · 2026Article
- Immunophenotypic, Cytogenetic, and Molecular Characterization of NUP98-Rearranged Pediatric Myeloid Neoplasms.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026Article
- Condensates in fusion oncoprotein-driven leukemia: new biology and therapeutic opportunities.Trends in cancer · 2026Review
- Menin Inhibitors in Acute Myeloid Leukemia: Clinical Integration, Resistance, and the Path Beyond Monotherapy.Cancers · 2026Review
- Discovery and preclinical activity of the menin-KMT2A inhibitor ziftomenib in acute leukemia models.Blood · 2026Article
- Menin inhibitors as a treatment for acute leukemia: from bench to the clinic.Blood neoplasia · 2026Review
- Co-option of lineage plasticity as a hallmark of multipotent acute leukemias.Blood neoplasia · 2026Review
- Chromosomal rearrangement-enhanced mRNA stability drives the oncogenic potential of fusion genes in pediatric leukemia.Haematologica · 2026Article
- The new era of AML therapy: current standards and emerging targets.International journal of clinical oncology · 2026Review
- Comprehensive mutational profiling and clinical outcome of adult acute myeloid leukemia patients with NUP98 rearrangement.Leukemia · 2026Article
- Downregulation of MLL1 Promotes Intestinal Epithelial Barrier Repair Through Gata4/Bmp4 Activation to Ameliorate Crohn's Disease-Like Colitis in Mice.Cell proliferation · 2026Article
- Developmental timing distinguishes pediatric and adult cancers through retention and rewiring mechanisms.Nature communications · 2026Review
- Menin Inhibition in Acute Myeloid Leukemia: Rewiring Leukemic Transcriptional Networks.International journal of molecular sciences · 2026Review
- Advances in targeted therapies for pediatric tumors.Acta pharmacologica Sinica · 2026Article
- Advancing precision therapy in pediatric acute myeloid leukemia through PDX models and mitochondrial targeting.Blood advances · 2026Article
- Optical genome mapping detects cryptic high-risk and targetable abnormalities in adult AML.British journal of haematology · 2026Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Translocations involving the NUP98 gene produce NUP98-fusion proteins and are associated with a poor prognosis in acute myeloid leukemia (AML). MLL1 is a molecular dependency in NUP98-fusion leukemia, and therefore we investigated the efficacy of therapeutic blockade of the menin-MLL1 interaction in NUP98-fusion leukemia models. Using mouse leukemia cell lines driven by NUP98-HOXA9 and NUP98-JARID1A fusion oncoproteins, we demonstrate that NUP98-fusion-driven leukemia is sensitive to the menin-MLL1 inhibitor VTP50469, with an IC50 similar to what we have previously reported for MLL-rearranged and NPM1c leukemia cells. Menin-MLL1 inhibition upregulates markers of differentiation such as CD11b and downregulates expression of proleukemogenic transcription factors such as Meis1 in NUP98-fusion-transformed leukemia cells. We demonstrate that MLL1 and the NUP98 fusion protein itself are evicted from chromatin at a critical set of genes that are essential for the maintenance of the malignant phenotype. In addition to these in vitro studies, we established patient-derived xenograft (PDX) models of NUP98-fusion-driven AML to test the in vivo efficacy of menin-MLL1 inhibition. Treatment with VTP50469 significantly prolongs survival of mice engrafted with NUP98-NSD1 and NUP98-JARID1A leukemias. Gene expression analysis revealed that menin-MLL1 inhibition simultaneously suppresses a proleukemogenic gene expression program, including downregulation of the HOXa cluster, and upregulates tissue-specific markers of differentiation. These preclinical results suggest that menin-MLL1 inhibition may represent a rational, targeted therapy for patients with NUP98-rearranged leukemias.
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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.