ArticleCell2025
Disparate leukemia mutations converge on nuclear phase-separated condensates.
Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Ptbp1 Condensates With Phase Separation-Like Features in Cardiomyocyte Nuclei Regulate Splicing of Proliferative Genes in Neonatal Cardiomyocytes.Development, growth & differentiation · 2026Article
- 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
- Article
- Menin inhibitors as a treatment for acute leukemia: from bench to the clinic.Blood neoplasia · 2026Review
- Convergent nuclear proteostasis alterations across 40S ribosomal protein deficiencies.Nature communications · 2026Article
- Multiaxial Biophysical Control of Oncogenic Phase Separation by Indoleamines: A Proof-of-Concept Synthesis of Landscape-Level Regulation.Journal of pineal research · 2026Review
- Single-molecule nucleosome spacing coordinates chromatin fiber interactions.bioRxiv : the preprint server for biology · 2026Article
- Mapping RNA structure assembly and remodeling in biomolecular condensates.bioRxiv : the preprint server for biology · 2026Article
- A unified photosensitizer platform forbioRxiv : the preprint server for biology · 2026Article
- A Unified Model: Chromatin-Bound Multicomponent Condensates.Cancer research · 2026Article
- Article
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Authors and funding
25 authors.
Funding
Abstract
During cancer development, mutations promote changes in gene expression that cause transformation. Leukemia associated with aberrant HOXA expression is driven by translocations of nucleoporin genes or KMT2A as well as mutations in NPM1. The mechanistic convergence of these disparate mutations remains elusive. Here, we demonstrate that mutant nucleophosmin 1 (NPM1c) forms nuclear condensates in human cell lines, mouse models, and primary patient samples. We show NPM1c phase separation is necessary and sufficient to recruit NUP98 and KMT2A to condensates. Through extensive mutagenesis and pharmacological destabilization of phase separation, we find that NPM1c condensates are necessary for regulating gene expression, promoting in vivo leukemic expansion, and maintaining the undifferentiated leukemic state. Finally, we show that nucleoporin and KMT2A fusion proteins form condensates that are biophysically indistinguishable from NPM1c condensates. Together, these data define a new condensate that we term the coordinating body (C-body) and establish C-bodies as a therapeutic vulnerability in leukemia.
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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.