ArticleLeukemia2025
NPM1-fusion proteins promote myeloid leukemogenesis through XPO1-dependent HOX activation.
Article in Leukemia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- NPM1-rearranged AML: clinical features, molecular pathogenesis, and therapeutic perspectives.International journal of hematology · 2026Review
- Beyond nuclear export: chromatin-bound XPO1/CRM1 as a transcriptional scaffold.International journal of hematology · 2026Review
- Article
- Targeting the nuclear export receptor exportin-1 in acute myeloid leukaemia: From biology to clinical translation.Clinical and translational medicine · 2026Review
- Combined Menin and XPO1 inhibition drive synergistic antileukemic activity inbioRxiv : the preprint server for biology · 2026Article
- NPM1c⁺-driven lncRNA dysregulation in AML: Mechanisms, Controversies and translational roadblocks.Translational oncology · 2026Review
- Review
- Tandem Duplications in UBTF Create XPO1-Dependent Nuclear Export Signals that Reveal a Leukemic Therapeutic Dependency.Blood cancer discovery · 2026Article
- Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy.NPJ precision oncology · 2025Review
- Concurrent NPM1::CCDC28A and BCR::ABL1 fusions in extramedullary blast crisis of chronic myeloid leukemia: A case report and literature review.Annals of hematology · 2025Review
- A Mutational Landscape in Acute Myeloid Leukemia: Overview and Prognostic Impacts.Diagnostics (Basel, Switzerland) · 2025Review
- NUP214 in Acute Myeloid Leukemia.Cells · 2025Review
- RAN potentiates nuclear export of phosphorylated AMPK, reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinoma.NPJ precision oncology · 2025Article
- Menin Inhibitors: New Targeted Therapies for Specific Genetic Subtypes of Difficult-to-Treat Acute Leukemias.Cancers · 2025Review
- Identification and experimental validation of demethylation-related genes in diabetic nephropathy.Frontiers in genetics · 2025Article
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Authors and funding
9 authors.
Funding
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Abstract
Nucleophosmin (NPM1) is a nucleolar protein and one of the most frequently mutated genes in acute myeloid leukemia (AML). In addition to the commonly detected frameshift mutations in exon12 (NPM1c), previous studies have identified NPM1 gene rearrangements leading to the expression of NPM1-fusion proteins in pediatric AML. However, whether the NPM1-fusions are indeed oncogenic and how the NPM1-fusions cause AML have been largely unknown. In this study, we investigated the subcellular localization and leukemogenic potential of two rare NPM1-fusion proteins, NPM1::MLF1 and NPM1::CCDC28A. NPM1::MLF1 is present in both the nucleus and cytoplasm and occasionally induces AML in the mouse transplantation assay. NPM1::CCDC28A is more localized to the cytoplasm, immortalizes mouse bone marrow cells in vitro and efficiently induces AML in vivo. Mechanistically, both NPM1-fusions bind to the HOX gene cluster and, like NPM1c, cause aberrant upregulation of HOX genes in cooperation with XPO1. The XPO1 inhibitor selinexor suppressed HOX activation and colony formation driven by the NPM1-fusions. NPM1::CCDC28A cells were also sensitive to menin inhibition. Thus, our study provides experimental evidence that both NPM1::MLF1 and NPM1::CCDC28A are oncogenes with functions similar to NPM1c. Inhibition of XPO1 and menin may be a promising strategy for the NPM1-rearranged AML.
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