The anti-leukemic and lipid lowering effects of imatinib are not hindered by statins in CML: a retrospective clinical study andin vitroassessment of lipid-genes transcription

Autor: Osnat Ashur-Fabian, Sarah Gan, Avishai Elis, Martin Ellis, Eilon Krashin, Orly Hamburger-Avnery
Rok vydání: 2016
Předmět:
Drug
Cancer Research
Transcription
Genetic
media_common.quotation_subject
Fusion Proteins
bcr-abl
Antineoplastic Agents
Pharmacology
Leukocyte Count
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
Leukemia
Myelogenous
Chronic
BCR-ABL Positive
hemic and lymphatic diseases
Transcriptional regulation
medicine
Humans
Protein Kinase Inhibitors
neoplasms
media_common
medicine.diagnostic_test
Gene Expression Regulation
Leukemic
business.industry
Myeloid leukemia
Drug Synergism
Imatinib
Hematology
Lipid Metabolism
medicine.disease
Lipids
In vitro
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Imatinib Mesylate
lipids (amino acids
peptides
and proteins)
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipid profile
business
Biomarkers
Dyslipidemia
030215 immunology
medicine.drug
K562 cells
Zdroj: Leukemia & Lymphoma. 58:1172-1177
ISSN: 1029-2403
1042-8194
DOI: 10.1080/10428194.2016.1228928
Popis: 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.
Databáze: OpenAIRE
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