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Role of Sphingolipids in Hematological Malignancies: Lymphoproliferative Disorders

  • Chapter
Bioactive Sphingolipids in Cancer Biology and Therapy

Abstract

Among sphingolipids, ceramide was first reported to induce cell differentiation and death in human leukemia cells. The localization of signaling ceramide, the putative different functions of ceramide species, and their metabolic regulation have been investigated in regard to induction of cell death of many types of cancers. Recently not only ceramide but also sphingosine-1-phosphate (S1P), sphingomyelin (SM) and ceramide-1-phosphate are being appreciated to act as biological lipid regulators of many cell functions. It is critical to understand the role of sphingolipids in the regulation of the balance between proliferation and cell death for developing novel therapies for hematological malignant diseases. Programmed cell death is mainly classified into four categories: apoptosis, regulated necrosis/necroptosis, pyroptosis and autophagic cell death. In this chapter, we summarize the role of ceramide and other sphingolipids in programmed cell death, proliferation/survival, differentiation, migration and secretion of lymphoid lineage cells to discuss potential applications of sphingolipid-based treatment for lymphoproliferative disorders such as acute and chronic lymphoid leukemia, malignant lymphoma and multiple myeloma.

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Acknowledgments

This study was supported by the Takeda Science Foundation (2012–2016), and performed with the joint research project with Shalome Co. (2012–2014), Ltd., and with ONO Pharmaceutical Co. Ltd. (2011–2014). This work was also supported in part by a grant from Strategic Research Foundation Grant-aided Project for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) (No. S1201004, 2012–2016) and from Kanazawa Medical University (2012–2013), Mizutani Foundation for Glycoscience (2013–2014), the Collaborative Research from Kanazawa Medical University (C2012-4, C2013-1. 2012–2013). We greatly appreciate Drs. Asano S. and Shakor A.B. kindly granting us the use of Figs. 4 and 5.

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Authors and Affiliations

  1. Department of Internal Medicine, Osaka Dental University, Osaka, 573-1121, Japan

    Hirofumi Sawai

  2. Medical Research Institute, Kanazawa Medical University, Ishikawa, 920-0293, Japan

    Makoto Taniguchi

  3. Division of Hematology/Immunology, Department of Medicine, Kanazawa Medical University, Ishikawa, 920-0293, Japan

    Toshiro Okazaki

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  1. Hirofumi Sawai
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  2. Makoto Taniguchi
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  3. Toshiro Okazaki
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Correspondence to Toshiro Okazaki .

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Editors and Affiliations

  1. Stony Brook University, Stony Brook Cancer Center, Stony Brook, New York, USA

    Yusuf A. Hannun

  2. Dept. of Physiology & Biophysics, Stony Brook University, Stony Brook, New York, USA

    Chiara Luberto

  3. Dept. of Medicine, Stony Brook University, Stony Brook, New York, USA

    Cungui Mao

  4. Dept. of Medicine, Stony Brook University, Stony Brook, New York, USA

    Lina Marie Obeid

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Sawai, H., Taniguchi, M., Okazaki, T. (2015). Role of Sphingolipids in Hematological Malignancies: Lymphoproliferative Disorders. In: Hannun, Y., Luberto, C., Mao, C., Obeid, L. (eds) Bioactive Sphingolipids in Cancer Biology and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-20750-6_2

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