A Step-wise, Deterministic and Fatal Mouse Model of Myeloid Neoplasm with Spontaneous Acquisition of Patient-relevant RTK–RAS Mutations Article Swipe
Marija A. Zarocsinceva
,
M. Saeed Qureshi
,
Nicola K. Wilson
,
George Giotopoulos
,
Katherine Sturgess
,
M. S. Vijayabaskar
,
Sarah Kinston
,
Ryan Asby
,
David J. Adams
,
Brian J.P. Huntly
,
Fernando J. Calero‐Nieto
,
Berthold Göttgens
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.18.665518
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.18.665518
Leukaemia arises through the stepwise transformation of healthy haematopoietic cells, yet the asymptomatic premalignant phase and its progression to overt disease remain poorly understood. To model this process, we engineered a patient-derived CEBPA mutation into Hoxb8-FL multipotent murine progenitors and transplanted them into syngeneic mice, capturing a clinically silent premalignant stage. All recipients developed overt disease after ∼12 months with 100% penetrance and all acquired secondary RTK–RAS mutations, often with identical amino acid changes to those in patients. Single-cell transcriptomics and phenotypic profiling showed that premalignant mutant cells adopt a plasmacytoid dendritic progenitor–like state in vitro which generates both myeloid and B-lymphoid lineages during premalignancy in vivo, with individual tumours restricted to one lineage. Specificity for RTK-RAS mutations coupled with ongoing differentiation is reminiscent of Juvenile Myelomonocytic Leukaemia, where cellular models are currently lacking, thus providing a tractable model of myeloid neoplasm for mechanistic studies and drug discovery.
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Concepts
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.07.18.665518
- https://www.biorxiv.org/content/biorxiv/early/2025/07/22/2025.07.18.665518.full.pdf
- OA Status
- green
- References
- 55
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412581527
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412581527Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.07.18.665518Digital Object Identifier
- Title
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A Step-wise, Deterministic and Fatal Mouse Model of Myeloid Neoplasm with Spontaneous Acquisition of Patient-relevant RTK–RAS MutationsWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-07-22Full publication date if available
- Authors
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Marija A. Zarocsinceva, M. Saeed Qureshi, Nicola K. Wilson, George Giotopoulos, Katherine Sturgess, M. S. Vijayabaskar, Sarah Kinston, Ryan Asby, David J. Adams, Brian J.P. Huntly, Fernando J. Calero‐Nieto, Berthold GöttgensList of authors in order
- Landing page
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https://doi.org/10.1101/2025.07.18.665518Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2025/07/22/2025.07.18.665518.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2025/07/22/2025.07.18.665518.full.pdfDirect OA link when available
- Concepts
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Set (abstract data type), Neoplasm, Mutation, Myeloid, Computer science, Cancer research, Biology, Genetics, Computational biology, Gene, Programming languageTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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55Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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