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

Abstract

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.

Keywords

• Acute lymphoblastic leukemia
• Sphingosine kinase 2
• Mouse models