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Review
, 38 (6), 482-95

Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies

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Review

Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies

Kazuyuki Kitatani et al. Mol Cells.

Abstract

Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1-phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal bio-modulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.

Keywords: ceramide; leukemia; lymphoma; sphingolipid; sphingomyelin.

Figures

Fig. 1.
Fig. 1.
Sphingolipid metabolism and subcellular compartmentalization. A diverse sphingolipids are synthesized and degraded through complex metabolizing pathways in each intracellular compartment. For example, SM (colored by yellow) is synthesized in Golgi apparatus by SMS1 and SMS2, and in plasma membrane by SMS2, and resides in endosomes, lysosomes, mitochondria and nucleus. Each SM is suggested to play a role as a regulator of micro-organelles and a source of other bioactive sphingolipids.

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