Journal of Glycomics & Lipidomics
Open Access
ISSN: 2153-0637
ISSN: 2153-0637
Carl Freter
Saint Louis University, USA
Keynote: J Glycomics Lipidomics
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, and is still considered an incurable disease because most patients generally relapse and eventually develop drug-resistance. Fludarabine (flu)-containing regimens have been evaluated as first-line therapy in high-risk leukemia patients. However, drug-resistance represents a serious barrier to successful clinical treatment and is the major cause of treatment failure for CLL patients. Altering lipid metabolism in cancer cells may be more deleterious to growth and chemo-resistance than in normal cells. We hypothesize that altering lipid metabolism in cancer cells may affect chemotherapeutic efficacy. Our goal is to establish flu-resistant leukemia cell lines, determine the alteration of lipid metabolism in flu-resistant leukemia clones, and modify lipid metabolism to enhance chemoand immunotherapeutic efficacy. MEC-2 cells, a CLL cell line, were used as a cell model. Flu-resistant clones were established by exposure to escalating concentrations of fludarabine, starting from 10 �¼M to 400 �¼M and cloned from these final survivors. MEC-2 cells and flu-resistant clones were characterized in terms of lethal dose (LD50) and several biomarkers. Using MEC- 2 cells and flu-resistant clones, we further analyzed and compared the differences in lipid metabolism. We found that: 1) There is a significant accumulation of glucosylceramide and reduction of sphingomyelin, and 2) An increase in triacylglycerol and free fatty acids and a decrease in phosphatidylcholine and phosphatidylethanolamine in flu-resistant clones. Our data indicated that flu-resistant clones lead to altered lipid compositions which could increase cell survival and reduce apoptosis. Understanding molecular mechanisms of lipid metabolism and modulation of their pathways could provide a novel strategy to overcome drug resistance.
Carl Freter, MD, PhD, FACP is the Director of the Division of Hematology and Oncology at Saint Louis University. He is a tenured Professor of Medicine, Interim Director of the Saint Louis University Cancer Center and the Rosalie Fusz Endowed Chair of Hematology. He is also the Director of the Fellowship Program in Hematology and Oncology. He has received his MD and PhD in Biochemistry from the Washington University School of Medicine. He did his internship and residency training from the Stanford University and fellowship in Hematology/Oncology from the National Cancer Institute at the NIH. He was the Co-director of the Ellis Fischel Cancer Center at the University of Missouri-Columbia, as well as the Director of the Division of Hematology and Oncology.
Email: Freterc@slu.edu