title: Dysregulation of fatty acid synthesis and glycolysis in non-Hodgkin lymphoma.
abstract: The metabolic differences between B-NHL and primary human B cells are poorly understood. Among human B-cell non-Hodgkin lymphomas (B-NHL), primary effusion lymphoma (PEL) is a unique subset that is linked to infection with Kaposi's sarcoma-associated herpesvirus (KSHV). We report that the metabolic profiles of primary B cells are significantly different from that of PEL. Compared with primary B cells, both aerobic glycolysis and fatty acid synthesis (FAS) are up-regulated in PEL and other types of nonviral B-NHL. We found that aerobic glycolysis and FAS occur in a PI3K-dependent manner and appear to be interdependent. PEL overexpress the fatty acid synthesizing enzyme, FASN, and both PEL and other B-NHL were much more sensitive to the FAS inhibitor, C75, than primary B cells. Our findings suggest that FASN may be a unique candidate for molecular targeted therapy against PEL and other B-NHL.
authors: Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: Aadra P
authors: AP
authors: Bhatt
authors: Sarah R
authors: SR
authors: Jacobs
authors: Alex J
authors: AJ
authors: Freemerman
authors: Liza
authors: L
authors: Makowski
authors: Jeffrey C
authors: JC
authors: Rathmell
authors: Dirk P
authors: DP
authors: Dittmer
authors: Blossom
authors: B
authors: Damania
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D001402:B-Lymphocytes / Q000378:metabolism*; D019295:Computational Biology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors; D005227:Fatty Acids / Q000096:biosynthesis*; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D054685:Lymphoma, Primary Effusion / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D015107:4-Butyrolactone; D064429:Fatty Acid Synthases; D005227:Fatty Acids; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; C546842:MTOR protein, human