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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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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
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author Xie, Vicki
Tong, Daochen
Wallington-Beddoe, Craig T.
Bradstock, Ken F.
Bendall, Linda J.
author_facet Xie, Vicki
Tong, Daochen
Wallington-Beddoe, Craig T.
Bradstock, Ken F.
Bendall, Linda J.
author_sort Xie, Vicki
collection PubMed
description 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.
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spelling pubmed-58000792018-02-13 Sphingosine kinase 2 supports the development of BCR/ABL-independent acute lymphoblastic leukemia in mice Xie, Vicki Tong, Daochen Wallington-Beddoe, Craig T. Bradstock, Ken F. Bendall, Linda J. Biomark Res Research 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. BioMed Central 2018-02-05 /pmc/articles/PMC5800079/ /pubmed/29441205 http://dx.doi.org/10.1186/s40364-018-0120-4 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Xie, Vicki
Tong, Daochen
Wallington-Beddoe, Craig T.
Bradstock, Ken F.
Bendall, Linda J.
Sphingosine kinase 2 supports the development of BCR/ABL-independent acute lymphoblastic leukemia in mice
title Sphingosine kinase 2 supports the development of BCR/ABL-independent acute lymphoblastic leukemia in mice
title_full Sphingosine kinase 2 supports the development of BCR/ABL-independent acute lymphoblastic leukemia in mice
title_fullStr Sphingosine kinase 2 supports the development of BCR/ABL-independent acute lymphoblastic leukemia in mice
title_full_unstemmed Sphingosine kinase 2 supports the development of BCR/ABL-independent acute lymphoblastic leukemia in mice
title_short Sphingosine kinase 2 supports the development of BCR/ABL-independent acute lymphoblastic leukemia in mice
title_sort sphingosine kinase 2 supports the development of bcr/abl-independent acute lymphoblastic leukemia in mice
topic Research
url 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
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