In vitro leukemia cell models of Ara-C resistance

Tadao Funato, Junko Satou, Yuko Nishiyama, Shinichi Fujimaki, Toshihiko Miura, Mitsuo Kaku, Takeshi Sasaki

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Cells of the human leukemia line K562 were continuously exposed to cytosine arabinoside (Ara-C) at increasing concentrations for 3 months. The resulting cell line, termed K562/AC, showed 48-fold resistance to Ara-C, compared with the parental K562 cells. The sensitivities of K562/AC to adriamycin (ADR), vincristine (VCR) and etoposide (VP16) were similar to those of parental K562. Gene analysis revealed that this cell line lacked expression of the deoxycytidine kinase (dCK) gene, which was evident in Ara- C-sensitive cells. As in K562 cells, multidrug resistance (MDR-1) and multidrug resistance protein (MRP) genes were not expressed in K562/AC. We also established an in vitro model of Ara-C resistance using phosphorothioate antisense oligonucleotides to dCK (dCK-AS). Treatment of K562 with dCK-AS caused decreased dCK expression and 6- to 10-fold increases in resistance to Ara-C, compared with that in cells treated with sense oligonucleotides to dCK (dCK-S) or in non-transfected cells. The cells described here may contribute to the study of a novel mechanism associated with Ara-C resistance, in which reduced dCK activity may play an important role. (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)535-541
Number of pages7
JournalLeukemia Research
Issue number6
Publication statusPublished - 2000 Jun


  • Antisense oligonucleotides
  • Cytosine arabinoside (Ara-C)
  • Deoxycytidine kinase (dCK)
  • Drug resistance
  • Human leukemia K562 cell
  • MDR-1

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


Dive into the research topics of 'In vitro leukemia cell models of Ara-C resistance'. Together they form a unique fingerprint.

Cite this