CBFβ-SMMHC–driven leukemogenesis requires enhanced RUNX1-DNA binding affinity in mice Article Swipe
Tao Zhen
,
Yaqiang Cao
,
Tongyi Dou
,
Yun Chen
,
Guadalupe Lopez
,
Ana Catarina Menezes
,
Xufeng Wu
,
John A. Hammer
,
Jun Cheng
,
Lisa Garrett
,
Stacie M. Anderson
,
Martha Kirby
,
Stephen Wincovitch
,
Bayu Sisay
,
Abdel G. Elkahloun
,
Di Wu
,
Lucio H. Castilla
,
Wei Yang
,
Jiansen Jiang
,
Keji Zhao
,
Paul Liu
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1172/jci192923
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1172/jci192923
The leukemia fusion gene CBFB-MYH11 requires RUNX1 for leukemogenesis, but the underlying mechanism is unclear. By in vitro studies, we found that CBFβ-SMMHC, the chimeric protein encoded by CBFB-MYH11, could enhance the binding affinity between RUNX1 and its target DNA. Increased RUNX1-DNA binding was also observed in myeloid progenitor cells from mice expressing CBFβ-SMMHC. Moreover, only CBFβ-SMMHC variants able to enhance the DNA binding affinity by RUNX1 could induce leukemia in mouse models. Marked transcriptomic changes, affecting genes associated with inflammatory response and target genes of CBFA2T3, were observed in mice expressing leukemogenic CBFβ-SMMHC variants. Finally, we show that CBFβ-SMMHC could not induce leukemia in mice with a Runx1-R188Q mutation, which reduces RUNX1 DNA binding but does not affect its interaction with CBFβ-SMMHC or its sequestration to cytoplasm by CBFβ-SMMHC. Our data suggest that, in addition to binding RUNX1 to regulate gene expression, enhancing RUNX1 binding affinity to its target DNA is an important mechanism by which CBFβ-SMMHC contributes to leukemogenesis, highlighting RUNX1-DNA interaction as a potential therapeutic target in inv(16) acute myeloid leukemia.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1172/jci192923
- http://www.jci.org/articles/view/192923/files/pdf
- OA Status
- gold
- References
- 72
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412984373
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412984373Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1172/jci192923Digital Object Identifier
- Title
-
CBFβ-SMMHC–driven leukemogenesis requires enhanced RUNX1-DNA binding affinity in miceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
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2025-08-05Full publication date if available
- Authors
-
Tao Zhen, Yaqiang Cao, Tongyi Dou, Yun Chen, Guadalupe Lopez, Ana Catarina Menezes, Xufeng Wu, John A. Hammer, Jun Cheng, Lisa Garrett, Stacie M. Anderson, Martha Kirby, Stephen Wincovitch, Bayu Sisay, Abdel G. Elkahloun, Di Wu, Lucio H. Castilla, Wei Yang, Jiansen Jiang, Keji Zhao, Paul LiuList of authors in order
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https://doi.org/10.1172/jci192923Publisher landing page
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https://www.jci.org/articles/view/192923/files/pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.jci.org/articles/view/192923/files/pdfDirect OA link when available
- Concepts
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RUNX1, DNA, Cell biology, Chemistry, Molecular biology, Biology, Transcription factor, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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72Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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