Molecular Plasticity Results in Oncofetal Reprogramming and Therapeutic Vulnerabilities in Juvenile Myelomonocytic Leukemia
Persistent fetal gene expression in pediatric malignancies is considered a consequence of prenatal maturation blockade. In this study, we demonstrate that oncogenic PTPN11 mutations enhance cellular plasticity. This leads to partial restoration of fetal molecular programs, creating new therapeutically exploitable vulnerabilities. See related commentary by Miao and Xu, pp. 168.
Authors
- Pavlo Lutsik (ORCID: https://orcid.org/0000-0001-9383-8555)
- Kai Tan (ORCID: https://orcid.org/0000-0002-9104-5567)
- Katharina Bauer
- Stefan Fröhling (ORCID: https://orcid.org/0000-0001-7907-4595)
- Marc Jan Bonder (ORCID: https://orcid.org/0000-0002-8431-3180)
- Christian Flotho (ORCID: https://orcid.org/0000-0001-9367-0553)
- Miriam Erlacher (ORCID: https://orcid.org/0000-0002-7261-1447)
- Mark Hartmann (ORCID: https://orcid.org/0000-0002-4072-4658)
- Daniel B. Lipka (ORCID: https://orcid.org/0000-0001-5081-7869)
- Christoph Plass (ORCID: https://orcid.org/0000-0003-2554-3952)
- Viktoria Flore (ORCID: https://orcid.org/0009-0001-3023-433X)
- Christian Buske (ORCID: https://orcid.org/0000-0002-9782-9012)
- Maximilian Schönung (ORCID: https://orcid.org/0000-0002-9778-9698)
- Elliot Stieglitz (ORCID: https://orcid.org/0000-0001-7032-4623)
- Simon Haas (ORCID: https://orcid.org/0000-0001-9227-2051)
- Sina Stäble (ORCID: https://orcid.org/0000-0002-5962-2440)
- Fatemeh Alikarami (ORCID: https://orcid.org/0000-0002-3600-9192)
- Jens Langstein (ORCID: https://orcid.org/0009-0005-4284-0854)
- Eleonora Khabirova (ORCID: https://orcid.org/0000-0002-5891-6789)
- Dirk Lebrecht (ORCID: https://orcid.org/0000-0002-4483-2920)
- Changya Chen (ORCID: https://orcid.org/0000-0003-4421-2462)
- Joschka Hey (ORCID: https://orcid.org/0000-0003-2842-764X)
- Valentin Maurer (ORCID: https://orcid.org/0000-0002-7670-0586)
- Abdul‐Habib Maag (ORCID: https://orcid.org/0009-0008-5835-2910)
- Mariam Hakobyan (ORCID: https://orcid.org/0000-0003-4719-5186)
- Jan‐Philipp Mallm (ORCID: https://orcid.org/0000-0002-7059-4030)
- Muzlifah A. Haniffa (ORCID: https://orcid.org/0000-0002-3927-2084)
- Sam Behjati (ORCID: https://orcid.org/0000-0002-6600-7665)
- Michael D. Milsom (ORCID: https://orcid.org/0000-0002-3567-254X)
- Roland Roelz (ORCID: https://orcid.org/0000-0002-0985-7583)
- Matthias Schlesner (ORCID: https://orcid.org/0000-0002-5896-4086)
- Dominik Vonficht (ORCID: https://orcid.org/0000-0002-5579-7083)
- Tobias Boch (ORCID: https://orcid.org/0000-0001-8588-4180)
- Laura Jardine (ORCID: https://orcid.org/0000-0003-4495-8205)
- Simon Raffel (ORCID: https://orcid.org/0000-0003-4671-1097)
- Kathrin M. Bernt (ORCID: https://orcid.org/0000-0002-0691-356X)
- Sheila Bohler (ORCID: https://orcid.org/0000-0001-8860-9424)
- Ling Hai (ORCID: https://orcid.org/0000-0001-8719-2727)
- Jun Wang (ORCID: https://orcid.org/0009-0005-6938-9821)
- Julia Meyer (ORCID: https://orcid.org/0000-0001-5945-9885)
- Charlotte M. Niemeyer (ORCID: https://orcid.org/0000-0003-3856-7937)
- Jovana Rajak (ORCID: https://orcid.org/0009-0007-0229-8583)
Institutions
- Helmholtz Association of German Research Centres (DE)
- Children's Hospital of Philadelphia (US)
- University of Freiburg (DE)
- Queen Mary University of London (GB)
- University of Augsburg (DE)
- German Cancer Research Center (DE)
- University of California, San Francisco (US)
- Universität Ulm (DE)
- Max Delbrück Center (DE)
- Heidelberg University (DE)
- University of Cambridge (GB)
- University Medical Center Freiburg (DE)
- University Hospital Heidelberg (DE)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Wellcome Sanger Institute (GB)
- Bridge University (SS)
- National Center for Tumor Diseases (DE)
- Institute of Human Genetics (PL)
- UCSF Benioff Children's Hospital (US)
- European Molecular Biology Laboratory (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- AstraZeneca (Canada) (CA)
- DKFZ-ZMBH Alliance (DE)
- Heidelberg Institute for Stem Cell Technology and Experimental Medicine (DE)
- European Molecular Biology Laboratory (DE)
- University Hospital Ulm (DE)
- University Medical Centre Mannheim (DE)
- Centre for Structural Systems Biology (DE)
- Medizinische Fakultät Mannheim
- Charité - Universitätsmedizin Berlin (DE)
- University of Pennsylvania (US)
- Newcastle University (GB)
- Epigenomics (Germany) (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
- KU Leuven (BE)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2025-12-05
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0246
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00