Defective expression of deoxycytidine kinase in cytarabine-resistant acute myeloid leukemia cells
- Authors
- Song, Ju Han; Kim, Seung Hyun; Kweon, Sin Ho; Lee, Tae Hyang; Kim, Hee-Je; Kim, Hyeoung-Joon; Kim, Tae Sung
- Issue Date
- Apr-2009
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- acute myeloid leukemia; cytarabine; deoxycytidine kinase; drug-resistance
- Citation
- INTERNATIONAL JOURNAL OF ONCOLOGY, v.34, no.4, pp.1165 - 1171
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF ONCOLOGY
- Volume
- 34
- Number
- 4
- Start Page
- 1165
- End Page
- 1171
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/120372
- DOI
- 10.3892/ijo_00000245
- ISSN
- 1019-6439
- Abstract
- 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.
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