Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML. Article Swipe
Silvia Basilico
,
Xiaonan Wang
,
Alison Kennedy
,
Konstantinos Tzelepis
,
George Giotopoulos
,
Sarah Kinston
,
Pedro M. Quirós
,
Kim Wong
,
David J. Adams
,
Larissa S. Carnevalli
,
Brian J.P. Huntly
,
George S. Vassiliou
,
Fernando J. Calero‐Nieto
,
Berthold Göttgens
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.17863/cam.51588
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.17863/cam.51588
Leukaemogenic mutations commonly disrupt cellular differentiation and/or enhance proliferation, thus perturbing the regulatory programs that control self-renewal and differentiation of stem and progenitor cells. Translocations involving the Mll1 (Kmt2a) gene generate powerful oncogenic fusion proteins, predominantly affecting infant and paediatric AML and ALL patients. The early stages of leukaemogenic transformation are typically inaccessible from human patients and conventional mouse models. Here, we take advantage of cells conditionally blocked at the multipotent haematopoietic progenitor stage to develop a MLL-r model capturing early cellular and molecular consequences of MLL-ENL expression based on a clear clonal relationship between parental and leukaemic cells. Through a combination of scRNA-seq, ATAC-seq and genome-scale CRISPR-Cas9 screening, we identify pathways and genes likely to drive the early phases of leukaemogenesis. Finally, we demonstrate the broad utility of using matched parental and transformed cells for small molecule inhibitor studies by validating both previously known and other potential therapeutic targets.
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- Type
- article
- Language
- en
- Landing Page
- https://www.repository.cam.ac.uk/handle/1810/304509
- OA Status
- green
- Related Works
- 20
- OpenAlex ID
- https://openalex.org/W3016877101
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3016877101Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.17863/cam.51588Digital Object Identifier
- Title
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Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML.Work title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2020Year of publication
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2020-03-16Full publication date if available
- Authors
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Silvia Basilico, Xiaonan Wang, Alison Kennedy, Konstantinos Tzelepis, George Giotopoulos, Sarah Kinston, Pedro M. Quirós, Kim Wong, David J. Adams, Larissa S. Carnevalli, Brian J.P. Huntly, George S. Vassiliou, Fernando J. Calero‐Nieto, Berthold GöttgensList of authors in order
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https://www.repository.cam.ac.uk/handle/1810/304509Publisher landing page
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.repository.cam.ac.uk/handle/1810/304509Direct OA link when available
- Concepts
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Biology, Haematopoiesis, Leukemia, Progenitor cell, Cancer research, Fusion gene, Oncogene, CRISPR, Chromosomal translocation, Gene, Stem cell, Genetics, Cell cycleTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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20Other works algorithmically related by OpenAlex
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