ArticleCancer discovery2023
Mutant NPM1 Directly Regulates Oncogenic Transcription 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 101 papers.
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Who cites it
101 citing papers in PubMed, 116 citations in OpenAlex.
- Ziftomenib in Relapsed or RefractoryJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
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- Two Decades ofCancers · 2026Review
- 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
- Signaling Mutations Negate the Favorable Impact of NPM1 Mutations in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Treated With VEN/HMA.American journal of hematology · 2026Article
- The interaction between NPMc+ and Orai1 induces abnormal calcium influx to facilitate leukemogenesis.The FEBS journal · 2026Article
- Beyond nuclear export: chromatin-bound XPO1/CRM1 as a transcriptional scaffold.International journal of hematology · 2026Review
- Article
- Blocking SETD2 Enhances the Therapeutic Efficiency of Menin Inhibitor in MLL-Fusion Leukemia.Cancer science · 2026Article
- Controversies in the Management of AML in Older Patients: A Canadian Perspective.Current oncology (Toronto, Ont.) · 2026Review
- Disrupting a Convergent Acetylation Circuit Collapses Leukemic Identity Across AML Subtypes.bioRxiv : the preprint server for biology · 2026Article
- Combining menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemia.Blood advances · 2026Article
- Epigenetic Regulation in Acute Myeloid Leukemia: Molecular Mechanisms and Clinical Implications.Cancers · 2026Review
- Targeting SMC3 deacetylation synergizes with XPO1 inhibition to reprogram the epigenetic landscape and suppress NPM1-mutated acute myeloid leukemia.Nature communications · 2026Article
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Menin Inhibition in Acute Myeloid Leukemia: Rewiring Leukemic Transcriptional Networks.International journal of molecular sciences · 2026Review
- Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 3 countries.
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Abstract
The dysregulation of developmental and stem cell-associated genes is a common phenomenon during cancer development. Around half of patients with acute myeloid leukemia (AML) express high levels of HOXA cluster genes and MEIS1. Most of these AML cases harbor an NPM1 mutation (NPM1c), which encodes for an oncoprotein mislocalized from the nucleolus to the cytoplasm. How NPM1c expression in hematopoietic cells leads to its characteristic gene-expression pattern remains unclear. Here, we show that NPM1c directly binds to specific chromatin targets, which are co-occupied by the histone methyltransferase KMT2A (MLL1). Targeted degradation of NPM1c leads to a rapid decrease in gene expression and loss of RNA polymerase II, as well as activating histone modifications at its targets. We demonstrate that NPM1c directly regulates oncogenic gene expression in collaboration with the MLL1 complex and define the mechanism by which MLL1-Menin small-molecule inhibitors produce clinical responses in patients with NPM1-mutated AML. SIGNIFICANCE: We uncovered an important functional role of mutant NPM1 as a crucial direct driver of oncogenic gene expression in AML. NPM1c can bind to chromatin and cooperate with the MLL complex, providing the first functional insight into the mechanism of Menin-MLL inhibition in NPM1c leukemias. See related article by Wang et al., p. 724. 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.