title: Characterization of newly established human myeloid leukemia cell line (KF-19) and its drug resistant sublines.
abstract: A new human myeloid leukemia cell line, designated KF-19, and its drug resistant sublines have been established. The KF-19 cell line was established from the pericardial effusion of a patient with acute myeloid leukemia clinically resistant to chemotherapy and KF-19 cells were characterized by expression of myeloid markers and differentiation into neutrophil- and macrophage-like cells upon optimal stimulations. KF-19AraC, KF-19ADR and KF-19VCR were established as sublines resistant to cytosine arabinoside (AraC), adriamycin (ADR) and vincristine (VCR), respectively. Efflux of the corresponding drugs was documented in each cell line. Expression of the MDR1 gene and the P-glycoprotein was found only in KF-19ADR, which showed a cross resistance to anthracyclines and vinca alkaloids; this resistance was reversed by verapamil or cyclosporin A. KF-19VCR lacking MDR1 gene and P-glycoprotein expression showed only resistance to vinca alkaloids, which was partially reversed by verapamil and cyclosporin A. Unexpectedly, KF-19ADR and KF-19VCR displayed cross resistance to AraC, despite lack of alterations of deoxycytidine kinase (dCK) and deaminase (dA) activities. KF-19AraC showed an efflux of AraC as well as a decreased level of dCK, but not of dA. In addition, KF-19AraC showed cross resistance to VCR in the efflux assay. The cell lines reported herein will provide new aspects on the mechanisms of drug resistance in leukemic cells.
authors.affiliation: Second Department of Pathology, Niigata University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Kamishima
authors.forename: T
authors.initials: T
authors.lastname: Kakihara
authors.forename: Y
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D003564:Cytidine Deaminase; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D003842:Deoxycytidine Kinase / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D009700:Nucleoside Deaminases / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D007375:Interleukin-1; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D003561:Cytarabine; D005047:Etoposide; D004317:Doxorubicin; D007371:Interferon-gamma; D016572:Cyclosporine; D014700:Verapamil; D005982:Glutathione Transferase; D003842:Deoxycytidine Kinase; D009700:Nucleoside Deaminases; D003564:Cytidine Deaminase; C011530:deoxycytidine deaminase; D004250:DNA Topoisomerases, Type II; D008727:Methotrexate