- Title
- T-cell acute lymphoblastic leukemia express a unique truncated FAT1 isoform that cooperates with NOTCH1 in leukemia development
- Creator
- de Bock, Charles E.; Down, Michelle; Baidya, Kinsha; Sweron, Bram; Boyd, Andrew W.; Fiers, Mark; Burns, Gordon F.; Molloy, Timothy J.; Lock, Richard B.; Soulier, Jean; Taghon, Tom; Van Vlierberghe, Pieter; Cools, Jan; Holst, Jeff; Thorne, Rick F.
- Relation
- Haematologica Vol. 104, Issue 5, p. e204-e207
- Publisher Link
- http://dx.doi.org/10.3324/haematol.2018.198424
- Publisher
- Fondazione Ferrata Storti
- Resource Type
- journal article
- Date
- 2019
- Description
- The human FAT1 gene was cloned over 20 years ago, but there has only been an incremental understanding of its functional role in cancer and developmental disorders. FAT1 is highly expressed in a large proportion of cases of T-cell acute lymphoblastic leukemia (T-ALL) and B-cell ALL compared to their normal counterparts suggesting an oncogenic function. Conversely, the FAT1 gene is also recurrently mutated in a small subset of TALL cases and also in chronic lymphocytic leukemia. Functionally, the FAT1 cadherin has been implicated in Wnt signaling, hippo signaling and more recently mitochondrial function which together suggests a role outside the classical cadherin function in regulating cell-cell adhesion. Here we show that T-ALL cell lines and clinical samples express a unique N-terminal truncated FAT1 mRNA transcript that generates a protein from a novel transcriptional start site within a retained intronic sequence. This novel transcript is regulated independently of full-length FAT1 and results in the expression of a truncated protein lacking almost the entire extracellular domain of FAT1. Significantly, this truncated protein is a novel biomarker for T-ALL and was found to cooperate with NOTCH in driving T-ALL in vivo, suggesting that in the context of T-ALL, this truncated protein may act as an oncogene.
- Subject
- T-cell; lymphoblastic leukemias; truncated FAT1 isoform; NOTCH1; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1429164
- Identifier
- uon:38689
- Identifier
- ISSN:0390-6078
- Rights
- This paper is published under a CC BY-NC 4.0 Creative Commons License. According to this license, an article may be copied, displayed, distributed, republished or otherwise reused provided the reuse is not an adaptation or a modification and the integrity of the original paper is maintained. This license does not allow for any kind of commercial use of the paper. https://creativecommons.org/licenses/by-nc/4.0/
- Language
- eng
- Full Text
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