title: Metabolism pathways in chronic lymphocytic leukemia.
abstract: Alterations in chronic lymphocytic leukemia (CLL) cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells' metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet the CLL cells' metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase (LPL) that mediates lipoprotein uptake and shifts the CLL cells' metabolism towards utilization of FFA. Herein, we review the evidence for altered lipid metabolism, increased mitochondrial activity and formation of reactive oxygen species (ROS) in CLL cells, and discuss the possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL.
authors.affiliation: a Division of Hematology , Davidoff Cancer Center, Rabin Medical Center , Petach Tikva , Israel ;|b The Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv , Israel ;
authors.forename: Uri
authors.initials: U
authors.lastname: Rozovski
authors.affiliation: c Department of Cell Research and Immunology , George S. Wise Faculty of Life Sciences, The Center for Nanoscience and Nanotechnology, Tel Aviv University , Tel Aviv , Israel ;
authors.forename: Inbal
authors.initials: I
authors.lastname: Hazan-Halevy
authors.affiliation: b The Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv , Israel ;|d Department of Hematology and Bone Marrow Transplantation , Tel-Aviv Sourasky Medical Center , Tel Aviv , Israel ;
authors.forename: Merav
authors.initials: M
authors.lastname: Barzilai
authors.affiliation: e Department of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.affiliation: e Department of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D050260:Carbohydrate Metabolism; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism*; D050356:Lipid Metabolism; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species
keywords: CLL; STAT3; lipoprotein lipase; metabolism; oxidative phosphorylation