Defective expression of deoxycytidine kinase in cytarabine-resistant acute myeloid leukemia cells

Ju Han Song, Seung Hyun Kim, Sin Ho Kweon, Tae Hyang Lee, Hee Je Kim, Hyeoung Joon Kim, Tae Sung Kim

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Resistance to cytarabine (Ara-C) incapacitates the therapeutic effort during the treatment of acute myeloid leukemia (AML). To elucidate mechanism responsible for the development of resistance to Ara-C, we established the Ara-C resistant AML-2/WT cell sublines, AML-2/IDAC and AML-2/ARC. We then conducted DNA microarray analysis to compare the AML-2/IDAC cells with parental AML-2/WT cells. The results of the microarray analysis revealed a severe defect in the expression of deoxycytidine kinase (dCK), which plays a key role in the transformation of Ara-C to the active form in AML-2/IDAC cells. A similar event was observed in AML-2/ARC cells, but not in Ara-C sensitive AML-2/IDA cells that were resistant to idarubicin. The decreased expression of dCK also resulted in lower activity in both Ara-C resistant variants. However, no significant difference in the intracellular concentration of Ara-C was observed among the cells tested, which indicates that the Ara-C resistant phenotype in our models occurred due to the lower expression and activity of dCK rather than a change in the ability to take up Ara-C. Additionally, in vitro assays using BM cells from AML patients revealed that the expression of dCK and the sensitivity to Ara-C were correlated. Taken together, these findings demonstrate that dCK can regulate the in vitro cellular response to Ara-C in AML cells.

Original languageEnglish
Pages (from-to)1165-1171
Number of pages7
JournalInternational journal of oncology
Issue number4
Publication statusPublished - 2009


  • Acute myeliod leukemia
  • Cytarabine
  • Deoxycytidine kinase
  • Drug-resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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