Creation of Philadelphia chromosome by CRISPR/Cas9-mediated double cleavages on BCR and ABL1 genes as a model for initial event in leukemogenesis Article Swipe
Minori Tamai
,
Shinichi Fujisawa
,
Thao Nguyen
,
Chiaki Komatsu
,
Keiko Kagami
,
Kenji Kamimoto
,
Kohei Omachi
,
Shin Kasai
,
Daisuke Harama
,
Atsushi Watanabe
,
Koshi Akahane
,
Kumiko Goi
,
Kazuhito Naka
,
Tadashi Kaname
,
Takanori Teshima
,
Takeshi Inukai
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-1437317/v1
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-1437317/v1
The Philadelphia (Ph) chromosome was the first translocation identified in leukemia. It is supposed to be generated by aberrant ligation between two DNA double-strand breaks (DSBs) at the BCR gene located on chromosome 9q34 and the ABL1 gene located on chromosome 22q11. Thus, mimicking the initiation process of translocation, we induced CRISPR/Cas9-mediated DSBs simultaneously at the breakpoints of the BCR and ABL1 genes in a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent human leukemia cell line. After transfection of two single guide RNAs (sgRNAs) targeting intron 13 of the BCR gene and intron 1 of the ABL1 gene, a factor-independent subline was obtained. In the subline, p210 BCR::ABL1 and its reciprocal ABL1::BCR fusions were generated as a result of balanced translocation corresponding to the Ph chromosome. Another set of sgRNAs targeting intron 1 of the BCR gene and intron 1 of the ABL1 gene induced a factor-independent subline expressing p190 BCR::ABL1. Both p210 and p190 BCR::ABL1 induced factor-independent growth by constitutively activating intracellular signaling pathways for transcriptional regulation of cell cycle progression and cell survival that are usually regulated by GM-CSF. These observations suggested that simultaneous DSBs at the BCR and ABL1 gene breakpoints are initiation events for oncogenesis in Ph + leukemia. (200/200 words)
Related Topics
Concepts
CRISPR
Event (particle physics)
Genetics
Gene
Biology
Philadelphia chromosome
Genome editing
breakpoint cluster region
Computational biology
Cancer research
Chromosomal translocation
Physics
Quantum mechanics
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-1437317/v1
- https://www.researchsquare.com/article/rs-1437317/latest.pdf
- OA Status
- gold
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4293136897
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4293136897Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.3.rs-1437317/v1Digital Object Identifier
- Title
-
Creation of Philadelphia chromosome by CRISPR/Cas9-mediated double cleavages on BCR and ABL1 genes as a model for initial event in leukemogenesisWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-06-08Full publication date if available
- Authors
-
Minori Tamai, Shinichi Fujisawa, Thao Nguyen, Chiaki Komatsu, Keiko Kagami, Kenji Kamimoto, Kohei Omachi, Shin Kasai, Daisuke Harama, Atsushi Watanabe, Koshi Akahane, Kumiko Goi, Kazuhito Naka, Tadashi Kaname, Takanori Teshima, Takeshi InukaiList of authors in order
- Landing page
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https://doi.org/10.21203/rs.3.rs-1437317/v1Publisher landing page
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https://www.researchsquare.com/article/rs-1437317/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.researchsquare.com/article/rs-1437317/latest.pdfDirect OA link when available
- Concepts
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CRISPR, Event (particle physics), Genetics, Gene, Biology, Philadelphia chromosome, Genome editing, breakpoint cluster region, Computational biology, Cancer research, Chromosomal translocation, Physics, Quantum mechanicsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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53Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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