Sphingolipid Metabolism and Leukemia: A Potential for Novel Therapeutic Approaches

Tara      Ann Burns; Chiara      Luberto

Abstract

Since the discovery and initial characterizations of sphingolipids (SLs) in 1884, extensive research has established that these molecules not only are structural components of eukaryotic membranes but they are also critical bioactive lipids involved in fundamental cellular processes such as proliferation, differentiation, apoptosis, inflammation, migration, and autophagy. Altered SL metabolism has been observed in many pathological conditions including hematological malignancies. Thus, targeting the SL pathway to induce lipid changes to counteract specific pathologies is currently being pursued as a promising, novel therapeutic intervention. In this review, we discuss the general characteristics of the SL pathway, illustrating those features relevant to the understanding of the role of SLs in leukemia, and we address novel SL-targeting therapeutic approaches.

Keywords: Sphingolipids, ceramide, sphingosine-1-phosphate, leukemia, ALL, CLL, LGL, AML, CML, SM, DAG, SPT