title: Antileukemic properties of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors.
abstract: Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors that act on the mevalonate pathway and inhibit synthesis of cholesterol, geranylgeranyl pyrophosphate (GGPP) and farnesyl pyrophosphate (FPP). In preclinical studies, these agents have been shown to inhibit proliferation, trigger apoptosis and promote cell differentiation of leukemia. Proposed mechanisms include cholesterol deprivation and inhibition of isoprenylation of important signaling molecules. Case reports and early clinical studies suggest a therapeutic potential for statins in acute myeloid leukemia (AML). In the other leukemias there are limited clinical data, but in vitro studies provide a strong rationale for future studies involving statins. The effects of statins on the immune system may lend these agents to a role in allogeneic stem cell transplant. While many of the studies are early, statins have the future potential to be integrated into conventional chemotherapy regimens with limited side effects.
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Northwestern University Medical School , Chicago, IL , USA.
authors.forename: Herman
authors.initials: H
authors.lastname: van Besien
authors.forename: Antonella
authors.initials: A
authors.lastname: Sassano
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Altman
authors.forename: Leonidas C
authors.initials: LC
authors.lastname: Platanias
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000188:drug therapy; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D007938:Leukemia / Q000188:drug therapy*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors