Defective expression of deoxycytidine kinase in cytarabine-resistant acute myeloid leukemia cells
| Autor: | Hee Je Kim, Hyeoung Joon Kim, Tae Hyang Lee, Seung Hyun Kim, Ju Han Song, Sin Ho Kweon, Tae Sung Kim |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Antimetabolites Antineoplastic Myeloid DNA Fragmentation Biology Models Biological Gene Expression Regulation Enzymologic hemic and lymphatic diseases Cell Line Tumor Deoxycytidine Kinase medicine Idarubicin Humans skin and connective tissue diseases Oligonucleotide Array Sequence Analysis Gene Expression Regulation Leukemic Cytarabine food and beverages Myeloid leukemia Deoxycytidine kinase biochemical phenomena metabolism and nutrition Cell cycle medicine.disease carbohydrates (lipids) Leukemia Leukemia Myeloid Acute medicine.anatomical_structure Phenotype Oncology Cell culture Drug Resistance Neoplasm Cancer research Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | International journal of oncology. 34(4) |
| ISSN: | 1019-6439 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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