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

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.

SUBMITTER: Xie V

PROVIDER: S-EPMC5800079 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Xie Vicki V Tong Daochen D Wallington-Beddoe Craig T CT Bradstock Ken F KF Bendall Linda J LJ

Biomarker research 20180205

<h4>Background</h4>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).<h4>Methods</h4>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 suppress ...[more]

PMID: 29441205

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