ALK ligand ALKAL2 potentiates MYCN‐driven neuroblastoma in the absence of ALK mutation
- Author
- Marcus Borenäs, Ganesh Umapathy, Wei‐Yun Lai, Dan E Lind, Barbara Witek, Jikui Guan, Patricia Mendoza‐Garcia, Tafheem Masudi, Arne Claeys (UGent) , Tzu‐Po Chuang, Abeer El Wakil, Badrul Arefin, Susanne Fransson, Jan Koster, Mathias Johansson, Jennie Gaarder, Jimmy Van den Eynden (UGent) , Bengt Hallberg and Ruth H Palmer
- Organization
- Abstract
- High-risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer. One indicator of high-risk NB is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable. Identification of anaplastic lymphoma kinase (ALK) as an NB oncogene raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in treatment of patients with activating ALK mutations. 8-10% of primary NB patients are ALK-positive, a figure that increases in the relapsed population. ALK is activated by the ALKAL2 ligand located on chromosome 2p, along with ALK and MYCN, in the "2p-gain" region associated with NB. Dysregulation of ALK ligand in NB has not been addressed, although one of the first oncogenes described was v-sis that shares > 90% homology with PDGF. Therefore, we tested whether ALKAL2 ligand could potentiate NB progression in the absence of ALK mutation. We show that ALKAL2 overexpression in mice drives ALK TKI-sensitive NB in the absence of ALK mutation, suggesting that additional NB patients, such as those exhibiting 2p-gain, may benefit from ALK TKI-based therapeutic intervention.
- Keywords
- General Biochemistry, Genetics and Molecular Biology, General Immunology and Microbiology, General Neuroscience, Molecular Biology, 2p-gain, ALK, ALKAL, MYCN, neuroblastoma, ANAPLASTIC LYMPHOMA KINASE, RECEPTOR TYROSINE KINASE, LARGE-CELL LYMPHOMA, INHIBITOR PF-06463922, ACTIVATING MUTATIONS, THERAPEUTIC TARGET, GROWTH-FACTOR, GENE, EXPRESSION, GENOME
Downloads
-
embj.2020105784.pdf
- full text (Published version)
- |
- open access
- |
- |
- 3.69 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8686831
- MLA
- Borenäs, Marcus, et al. “ALK Ligand ALKAL2 Potentiates MYCN‐driven Neuroblastoma in the Absence of ALK Mutation.” EMBO JOURNAL, vol. 40, no. 3, 2021, doi:10.15252/embj.2020105784.
- APA
- Borenäs, M., Umapathy, G., Lai, W., Lind, D. E., Witek, B., Guan, J., … Palmer, R. H. (2021). ALK ligand ALKAL2 potentiates MYCN‐driven neuroblastoma in the absence of ALK mutation. EMBO JOURNAL, 40(3). https://doi.org/10.15252/embj.2020105784
- Chicago author-date
- Borenäs, Marcus, Ganesh Umapathy, Wei‐Yun Lai, Dan E Lind, Barbara Witek, Jikui Guan, Patricia Mendoza‐Garcia, et al. 2021. “ALK Ligand ALKAL2 Potentiates MYCN‐driven Neuroblastoma in the Absence of ALK Mutation.” EMBO JOURNAL 40 (3). https://doi.org/10.15252/embj.2020105784.
- Chicago author-date (all authors)
- Borenäs, Marcus, Ganesh Umapathy, Wei‐Yun Lai, Dan E Lind, Barbara Witek, Jikui Guan, Patricia Mendoza‐Garcia, Tafheem Masudi, Arne Claeys, Tzu‐Po Chuang, Abeer El Wakil, Badrul Arefin, Susanne Fransson, Jan Koster, Mathias Johansson, Jennie Gaarder, Jimmy Van den Eynden, Bengt Hallberg, and Ruth H Palmer. 2021. “ALK Ligand ALKAL2 Potentiates MYCN‐driven Neuroblastoma in the Absence of ALK Mutation.” EMBO JOURNAL 40 (3). doi:10.15252/embj.2020105784.
- Vancouver
- 1.Borenäs M, Umapathy G, Lai W, Lind DE, Witek B, Guan J, et al. ALK ligand ALKAL2 potentiates MYCN‐driven neuroblastoma in the absence of ALK mutation. EMBO JOURNAL. 2021;40(3).
- IEEE
- [1]M. Borenäs et al., “ALK ligand ALKAL2 potentiates MYCN‐driven neuroblastoma in the absence of ALK mutation,” EMBO JOURNAL, vol. 40, no. 3, 2021.
@article{8686831,
abstract = {{High-risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer. One indicator of high-risk NB is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable. Identification of anaplastic lymphoma kinase (ALK) as an NB oncogene raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in treatment of patients with activating ALK mutations. 8-10% of primary NB patients are ALK-positive, a figure that increases in the relapsed population. ALK is activated by the ALKAL2 ligand located on chromosome 2p, along with ALK and MYCN, in the "2p-gain" region associated with NB. Dysregulation of ALK ligand in NB has not been addressed, although one of the first oncogenes described was v-sis that shares > 90% homology with PDGF. Therefore, we tested whether ALKAL2 ligand could potentiate NB progression in the absence of ALK mutation. We show that ALKAL2 overexpression in mice drives ALK TKI-sensitive NB in the absence of ALK mutation, suggesting that additional NB patients, such as those exhibiting 2p-gain, may benefit from ALK TKI-based therapeutic intervention.}},
articleno = {{e105784}},
author = {{Borenäs, Marcus and Umapathy, Ganesh and Lai, Wei‐Yun and Lind, Dan E and Witek, Barbara and Guan, Jikui and Mendoza‐Garcia, Patricia and Masudi, Tafheem and Claeys, Arne and Chuang, Tzu‐Po and El Wakil, Abeer and Arefin, Badrul and Fransson, Susanne and Koster, Jan and Johansson, Mathias and Gaarder, Jennie and Van den Eynden, Jimmy and Hallberg, Bengt and Palmer, Ruth H}},
issn = {{0261-4189}},
journal = {{EMBO JOURNAL}},
keywords = {{General Biochemistry,Genetics and Molecular Biology,General Immunology and Microbiology,General Neuroscience,Molecular Biology,2p-gain,ALK,ALKAL,MYCN,neuroblastoma,ANAPLASTIC LYMPHOMA KINASE,RECEPTOR TYROSINE KINASE,LARGE-CELL LYMPHOMA,INHIBITOR PF-06463922,ACTIVATING MUTATIONS,THERAPEUTIC TARGET,GROWTH-FACTOR,GENE,EXPRESSION,GENOME}},
language = {{eng}},
number = {{3}},
title = {{ALK ligand ALKAL2 potentiates MYCN‐driven neuroblastoma in the absence of ALK mutation}},
url = {{http://doi.org/10.15252/embj.2020105784}},
volume = {{40}},
year = {{2021}},
}
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: