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

• Main Authors: Vicki Xie, Daochen Tong, Craig T. Wallington-Beddoe, Ken F. Bradstock, Linda J. Bendall
• Format: Article
• Language: English
• Published: BMC 2018-02-01
• Series: Biomarker Research
• Subjects: Acute lymphoblastic leukemia; Sphingosine kinase 2; Mouse models
• Online Access: http://link.springer.com/article/10.1186/s40364-018-0120-4

Abstract 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.