title: The anti-leukemic and lipid lowering effects of imatinib are not hindered by statins in CML: a retrospective clinical study and in vitro assessment of lipid-genes transcription.
abstract: Imatinib, which has revolutionized chronic myeloid leukemia (CML) treatment, was suggested to improve lipid profile. Statins, a dyslipidemia drug, were reported to potentiate imatinib's antileukemic effect. However, analysis of imatinib combined with statins is lacking. We have retrospectively analyzed the normalization period of bcr-abl, blood counts, and lipids in 40 CML patients, 19 of which co-treated with statins, during short (<12 months) and prolonged (>12 months) imatinib treatment. Prior statins treatment did not hinder nor sensitized imatinib's anti-leukemic and lipid-lowering effects. CML cells (K562) treated with 1μM imatinib (24-96 h) were further assessed for the expression of central lipid-related genes by real-time PCR. HMGCoAR, LDL-R, and apobec1 expressions were significantly increased while CETP declined after 48-96 h. To conclude, imatinib produces an independent favorable lipid profile, which is not hindered by statins and is partly mediated via transcription regulation of genes involved in the clearance of plasma lipids.
authors.affiliation: a Translational Hemato-Oncology Laboratory , Hematology Institute and Blood Bank, Meir Medical Center , Kfar-Saba , Israel.|b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Martin
authors.initials: M
authors.lastname: Ellis
authors.affiliation: c Department of Internal Medicine A , Meir Medical Center , Kfar-Saba , Israel.
authors.forename: Eilon
authors.initials: E
authors.lastname: Krashin
authors.affiliation: a Translational Hemato-Oncology Laboratory , Hematology Institute and Blood Bank, Meir Medical Center , Kfar-Saba , Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Hamburger-Avnery
authors.affiliation: a Translational Hemato-Oncology Laboratory , Hematology Institute and Blood Bank, Meir Medical Center , Kfar-Saba , Israel.|b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gan
authors.affiliation: b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.|d Department of Internal Medicine C , Beilinson Campus, Rabin Medical Center , Petah Tikva , Israel.
authors.forename: Avishai
authors.initials: A
authors.lastname: Elis
authors.affiliation: a Translational Hemato-Oncology Laboratory , Hematology Institute and Blood Bank, Meir Medical Center , Kfar-Saba , Israel.|e The Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Osnat
authors.initials: O
authors.lastname: Ashur-Fabian
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers; D045744:Cell Line, Tumor; D004357:Drug Synergism; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000068877:Imatinib Mesylate / Q000494:pharmacology / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008055:Lipids / Q000097:blood; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D014158:Transcription, Genetic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: CML; Imatinib; lipids; statins