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Quantitative RT-PCR analysis of sphingolipid metabolic enzymes in acute leukemia and myelodysplastic syndromes

Leukemia volume 20, pages 2042–2046 (2006)Cite this article

Sphingolipids and their metabolites recently appeared as a potent class of regulators of cell proliferation, survival as well as apoptosis.1 The ceramide/S1P rheostat has been proposed as the model to determine the cell's fate.2 This rheostat is being increasingly recognized as a critical element in tumor cell proliferation and chemotherapy. Sphingomyelinase is responsible for the first step of the sphingomyelin-catabolic pathway and produces ceramide, which figures mostly as the proapoptic factor in response to various reagents including anti-cancer drug or radiation. On the contrary, sphingosine kinase (SPHK) is the enzyme that produces sphingosine 1–phosphate (S1P) from sphingosine. S1P binds to five G-protein coupled receptors called S1P receptors. S1P promotes cell survival or motion as the first or second cellular messenger in response to various agonists. Therefore, enzymes in this pathway provide potential targets for new anti-cancer drugs.

Interestingly, overexpression of SPHK1 is thought to be oncogenic, and renders transfected cells chemoresistant.2 SPHK1 mRNA was significantly higher in various cancer tissues than in their normal counterparts.3 In prostate cancer cell lines, we reported the inverse relationship between SPHK1 level and anti-cancer drug sensitivity.4 The quantity of each cellular sphingolipid metabolite was thought to be determined by the complex balance between each metabolic enzyme activity and substrate. However, no analysis of gene expression of sphingolipid metabolizing enzymes including SPHK1 of acute leukemia or related diseases has been reported.

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Acknowledgements

We express sincere thanks to Professor S Nakamura and other members of the Department of Laboratory Medicine, Nagoya University School of Medicine for their assistance. This work was partially supported by the Health and Labor Sciences Research Grants for the Research on Measures for Intractable Diseases from the Ministry of Health, Labor and Welfare.

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Authors and Affiliations

  1. Department of Medical Technology, Nagoya University Graduate School of Health Sciences, Nagoya University School of Health Sciences, Nagoya, Japan

    S Sobue, T Iwasaki, C Sugisaki, K Nagata, R Kikuchi, M Murakami, A Takagi, T Kojima & T Murate

  2. Department of Biochemistry, Gifu University School of Medicine, Gifu, Japan

    Y Banno

  3. Gifu International Institute of Biotechnology, Gifu, Japan

    Y Akao & Y Nozawa

  4. Department of Molecular Pathology, Aichi Cancer Center, Nagoya, Japan

    R Kannagi

  5. Department of Molecular Carcinogenesis, Nagoya University Graduate School of Medicine, Nagoya, Japan

    M Suzuki

  6. Department of Hematology Oncology, Nagoya University School of Medicine, Nagoya, Japan

    A Abe & T Naoe

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Sobue, S., Iwasaki, T., Sugisaki, C. et al. Quantitative RT-PCR analysis of sphingolipid metabolic enzymes in acute leukemia and myelodysplastic syndromes. Leukemia 20, 2042–2046 (2006). https://doi.org/10.1038/sj.leu.2404386

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