ArticleCancer discovery2023
Mutant NPM1 Hijacks Transcriptional Hubs to Maintain Pathogenic Gene Programs in Acute Myeloid Leukemia.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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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.
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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
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Impact of secondary-type mutations on the prognosis of AML patients with NPM1 mutation: a systematic review and meta-analysis.Annals of hematology · 2025Pooled it
- Ziftomenib in Relapsed or RefractoryJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Trial
- Nuclear mechanobiology rules immune cells' functions: from differentiation to cell trafficking and pathogen killing.Nucleus (Austin, Tex.) · 2026Review
- How do low-complexity domain interactions control transcription?Biochemical Society transactions · 2026Review
- Article
- Targeting Exportin-1 in Cancer: From Nuclear Export to Oncogenic Transcriptional Hubs.JMA journal · 2026Review
- NPM1-rearranged AML: clinical features, molecular pathogenesis, and therapeutic perspectives.International journal of hematology · 2026Review
- Condensates in fusion oncoprotein-driven leukemia: new biology and therapeutic opportunities.Trends in cancer · 2026Review
- CD73 inhibitor enhances the antitumor activity of selinexor in multiple myeloma by restoring the activation of CD8Cancer gene therapy · 2026Article
- Beyond nuclear export: chromatin-bound XPO1/CRM1 as a transcriptional scaffold.International journal of hematology · 2026Review
- Menin inhibitors as a treatment for acute leukemia: from bench to the clinic.Blood neoplasia · 2026Review
- Article
- Current Challenges of Transcription Compartmentalization Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Controversies in the Management of AML in Older Patients: A Canadian Perspective.Current oncology (Toronto, Ont.) · 2026Review
- Combining menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemia.Blood advances · 2026Article
- Disrupting a Convergent Acetylation Circuit Collapses Leukemic Identity Across AML Subtypes.bioRxiv : the preprint server for biology · 2026Article
- Targeting SMC3 deacetylation synergizes with XPO1 inhibition to reprogram the epigenetic landscape and suppress NPM1-mutated acute myeloid leukemia.Nature communications · 2026Article
- Menin Inhibition in Acute Myeloid Leukemia: Rewiring Leukemic Transcriptional Networks.International journal of molecular sciences · 2026Review
- Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 2 countries.
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Abstract
Nucleophosmin (NPM1) is a ubiquitously expressed nucleolar protein with a wide range of biological functions. In 30% of acute myeloid leukemia (AML), the terminal exon of NPM1 is often found mutated, resulting in the addition of a nuclear export signal and a shift of the protein to the cytoplasm (NPM1c). AMLs carrying this mutation have aberrant expression of the HOXA/B genes, whose overexpression leads to leukemogenic transformation. Here, for the first time, we comprehensively prove that NPM1c binds to a subset of active gene promoters in NPM1c AMLs, including well-known leukemia-driving genes-HOXA/B cluster genes and MEIS1. NPM1c sustains the active transcription of key target genes by orchestrating a transcription hub and maintains the active chromatin landscape by inhibiting the activity of histone deacetylases. Together, these findings reveal the neomorphic function of NPM1c as a transcriptional amplifier for leukemic gene expression and open up new paradigms for therapeutic intervention. SIGNIFICANCE: NPM1 mutation is the most common mutation in AML, yet the mechanism of how the mutant protein results in AML remains unclear. Here, for the first time, we prove mutant NPM1 directly binds to active chromatin regions and hijacks the transcription of AML-driving genes. See related article by Uckelmann et al., p. 746. This article is highlighted in the In This Issue feature, p. 517.
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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.