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Sphingosine kinase 2 supports the development of BCR/ABL-independent acute lymphoblastic leukemia in mice

BACKGROUND: Sphingosine kinase (SphK) 2 has been implicated in the development of a range of cancers and inhibitors of this enzyme are currently in clinical trial. We have previously demonstrated a role for SphK2 in the development of acute lymphoblastic leukemia (ALL). METHODS: In this and our prev...

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Detalles Bibliográficos
Autores principales: Xie, Vicki, Tong, Daochen, Wallington-Beddoe, Craig T., Bradstock, Ken F., Bendall, Linda J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800079/
https://www.ncbi.nlm.nih.gov/pubmed/29441205
http://dx.doi.org/10.1186/s40364-018-0120-4
Descripción
Sumario:BACKGROUND: Sphingosine kinase (SphK) 2 has been implicated in the development of a range of cancers and inhibitors of this enzyme are currently in clinical trial. We have previously demonstrated a role for SphK2 in the development of acute lymphoblastic leukemia (ALL). METHODS: In this and our previous study we use mouse models: in the previous study the disease was driven by the proto-oncogene BCR/ABL1, while in this study cancer risk was elevated by deletion of the tumor suppressor ARF. RESULTS: Mice lacking ARF and SphK2 had a significantly reduced incidence of ALL compared mice with wild type SphK2. CONCLUSIONS: These results show that the role of SphK2 in ALL development is not limited to BCR/ABL1 driven disease extending the potential use of inhibitors of this enzyme to ALL patients whose disease have driver mutations other than BCR/ABL1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40364-018-0120-4) contains supplementary material, which is available to authorized users.