Treatment of acute myeloid leukemia models by targeting a cell surface RNA-binding protein Article Swipe

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Benson M. George , Maria Eleftheriou , Eliza Yankova , Jonathan Perr , Peiyuan Chai , Gianluca Nestola , Karim Almahayni , Siân Evans , Aristi Damaskou , Helena Hemberger , Charlotta G. Lebedenko , Justyna Rak , Qi Yu , Ece Bapcum , James Russell , Jaana Bagri , Regan Volk , Malte Spiekermann , Richard M. Stone , George Giotopoulos , Brian J.P. Huntly , E. Joanna Baxter , Fernando D. Camargo , Jie Liu , Balyn W. Zaro , George S. Vassiliou , Leonhard Möckl , Jorge de la Rosa , Ryan A. Flynn , Konstantinos Tzelepis ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.1038/s41587-025-02648-2

Immunotherapies for acute myeloid leukemia (AML) and other cancers are limited by a lack of tumor-specific targets. Here we discover that RNA-binding proteins and glycosylated RNAs (glycoRNAs) form precisely organized nanodomains on cancer cell surfaces. We characterize nucleophosmin (NPM1) as an abundant cell surface protein (csNPM1) on a variety of tumor types. With a focus on AML, we observe csNPM1 on blasts and leukemic stem cells but not on normal hematopoietic stem cells. We develop a monoclonal antibody to target csNPM1, which exhibits robust anti-tumor activity in multiple syngeneic and xenograft models of AML, including patient-derived xenografts, without observable toxicity. We find that csNPM1 is expressed in a mutation-agnostic manner on primary AML cells and may therefore offer a general strategy for detecting and treating AML. Surface profiling and in vivo work also demonstrate csNPM1 as a target on solid tumors. Our data suggest that csNPM1 and its neighboring glycoRNA–cell surface RNA-binding protein (csRBP) clusters may serve as an alternative antigen class for therapeutic targeting or cell identification.

Related Topics

Acute Myeloid Leukemia

Concepts

NPM1 Myeloid leukemia Cancer research Haematopoiesis RNA Leukemia Monoclonal antibody Myeloid Biology Stem cell Antibody Immunology Cell biology Gene Biochemistry Karyotype Chromosome

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Type: article
Language: en
Landing Page: https://doi.org/10.1038/s41587-025-02648-2
PDF: https://www.nature.com/articles/s41587-025-02648-2.pdf
OA Status: hybrid
Cited By: 8
References: 67
Related Works: 10
OpenAlex ID: https://openalex.org/W4409704822

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DOI: https://doi.org/10.1038/s41587-025-02648-2

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Title: Treatment of acute myeloid leukemia models by targeting a cell surface RNA-binding protein

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Type: article

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Language: en

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Publication year: 2025

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Publication date: 2025-04-23

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Authors: Benson M. George, Maria Eleftheriou, Eliza Yankova, Jonathan Perr, Peiyuan Chai, Gianluca Nestola, Karim Almahayni, Siân Evans, Aristi Damaskou, Helena Hemberger, Charlotta G. Lebedenko, Justyna Rak, Qi Yu, Ece Bapcum, James Russell, Jaana Bagri, Regan Volk, Malte Spiekermann, Richard M. Stone, George Giotopoulos, Brian J.P. Huntly, E. Joanna Baxter, Fernando D. Camargo, Jie Liu, Balyn W. Zaro, George S. Vassiliou, Leonhard Möckl, Jorge de la Rosa, Ryan A. Flynn, Konstantinos Tzelepis

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Landing page: https://doi.org/10.1038/s41587-025-02648-2

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PDF URL: https://www.nature.com/articles/s41587-025-02648-2.pdf

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Concepts: NPM1, Myeloid leukemia, Cancer research, Haematopoiesis, RNA, Leukemia, Monoclonal antibody, Myeloid, Biology, Stem cell, Antibody, Immunology, Cell biology, Gene, Biochemistry, Karyotype, Chromosome

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Cited by: 8

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References (count): 67

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