title: Inhibitory effects of imatinib on vitamin D₃ synthesis in human keratinocytes.
abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of the BCR‑ABL1 fusion gene, a constitutively active, oncogenic tyrosine kinase that is responsible for the clinical features of CML. Tyrosine kinase inhibitors, such as imatinib, have markedly altered the treatment of CML. However, tyrosine kinase inhibitors are associated with side effects on bone metabolism, in adult and pediatric patients. Vitamin D3 is involved in the complex cycle of bone remodeling, therefore the present study aimed to investigate the influence of imatinib on vitamin D3 metabolism in the HaCaT human keratinocyte cell line, using commercially available enzyme assays. Imatinib was shown to significantly reduce the production of calcidiol and calcitriol. Based on interaction studies of imatinib with the cytochrome P450 (CYP450) inhibitors VID400 and ketoconazole, it is proposed that imatinib may interfere with the vitamin D3 cascade due to its metabolism by CYP27B1, which is involved in vitamin D3 metabolism.
authors.affiliation: Department of Dermatology, University Hospital Carl Gustav Carus, Dresden University of Technology, D‑01307 Dresden, Germany.
authors.forename: Lysann Michaela
authors.initials: LM
authors.lastname: Mehlig
authors.affiliation: Department of Dermatology, University Hospital Carl Gustav Carus, Dresden University of Technology, D‑01307 Dresden, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Garve
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology and Oncology, University Hospital Carl Gustav Carus, Dresden University of Technology, D‑01307 Dresden, Germany.
authors.forename: Josephine Tabea
authors.initials: JT
authors.lastname: Tauer
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology and Oncology, University Hospital Carl Gustav Carus, Dresden University of Technology, D‑01307 Dresden, Germany.
authors.forename: Meinolf
authors.initials: M
authors.lastname: Suttorp
authors.affiliation: Department of Dermatology, University Hospital Carl Gustav Carus, Dresden University of Technology, D‑01307 Dresden, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bauer
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002117:Calcitriol / Q000096:biosynthesis; D002460:Cell Line; D002762:Cholecalciferol / Q000096:biosynthesis*; D006801:Humans; D000068877:Imatinib Mesylate; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D002762:Cholecalciferol; D000068877:Imatinib Mesylate; D002117:Calcitriol