Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2

Misaki Kawasoe, Yasuko Yamamoto, Katsuya Okawa, Tadao Funato, Mayu Takeda, Takeshi Hara, Hisashi Tsurumi, Hisataka Moriwaki, Yuko Arioka, Masao Takemura, Hidetoshi Matsunami, Sanford P. Markey, Kuniaki Saito

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Abstract

The elucidation of drug resistance mechanisms is important in the development of clinical therapies for the treatment of leukemia. To study the drug resistance mechanisms, protein expression profiles of 1-β-D-arabinofuranosylcytosine (AraC)-sensitive K562 (K562S) cells and AraC-resistant K562 (K562AC) cells were compared using two-dimensional fluorescence difference gel electrophoresis. In a comparison of protein expression profiles, 2073 protein spots were found to be altered, and 15 proteins of them were remarkably altered. These proteins were identified by mass spectrometry. The most differently expressed proteins were aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and vimentin. Both proteins were verified using reverse transcriptase polymerase chain reaction and Western blot analysis. ALDH1A2 protein was found to be effective in AraC resistance. ALDH1A2 knock-down induced sensitivity to AraC treatment in K562AC cells, and ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Furthermore, the findings also suggest that ALDH1A2 expression is increased after the appearance of AraC resistance in clinical cases. These results will be helpful in understanding the mechanism of AraC resistance.

Original languageEnglish
Pages (from-to)597-603.e2
JournalExperimental Hematology
Volume41
Issue number7
DOIs
Publication statusPublished - 07-2013

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

Cite this

Kawasoe, M., Yamamoto, Y., Okawa, K., Funato, T., Takeda, M., Hara, T., Tsurumi, H., Moriwaki, H., Arioka, Y., Takemura, M., Matsunami, H., Markey, S. P., & Saito, K. (2013). Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2. Experimental Hematology, 41(7), 597-603.e2. https://doi.org/10.1016/j.exphem.2013.03.004