Characterization of cytarabine-resistant leukemic cell lines established from five different blood cell lineages using gene expression and proteomic analyses

  • Authors:
    • Eiju Negoro
    • Takahiro Yamauchi
    • Yoshimasa Urasaki
    • Rie Nishi
    • Hiroki Hori
    • Takanori Ueda
  • View Affiliations

  • Published online on: February 2, 2011     https://doi.org/10.3892/ijo.2011.933
  • Pages: 911-919
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Abstract

Cytarabine (ara-C) is the key drug for treatment of acute myeloid leukemia. Since intracellular cytarabine triphosphate (ara-CTP) is an active metabolite of ara-C, factors that reduce the amount of ara-CTP are known to induce drug resistance. However, these factors do not fully explain the development of resistance to ara-C. The present study was conducted to search for new candidate ara-C resistance factors, including those that are unrelated to ara-CTP production. For this purpose, we newly established five ara-C-resistant leukemic clones from different blood cell lineage leukemic cell lines (HL-60, K562, CEM, THP1 and U937). The resistant subclones were 5-58-fold more ara-C-resistant than their parental counterparts. All of the ara-C-resistant subclones, except for ara-C-resistant CEM cells, displayed alteration of ara-CTP-related factors such as ara-C membrane transport capacity, deoxycytidine kinase activity or cytosolic nucleotidase II activity. To identify new candidate factors, we used two comprehensive approaches: DNA microarray and proteome analyses. The DNA microarray analysis revealed eight genes (C19orf2, HSPA8, LGALS1, POU4F3, PSAP, AKT1, MBC2 and CACNA2D3) that were altered in all five ara-C-resistant lines compared to parental cells. Both proteome and DNA microarray analyses further detected a reduced protein level of stathmin1 in the ara-C-resistant CEM subclone compared to its parental line. Thus, the present findings suggested the involvement of novel multiple mechanisms in mediating the ara-C resistance of leukemic cells. The role of some of these molecules in resistance is still unclear.

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April 2011
Volume 38 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Negoro, E., Yamauchi, T., Urasaki, Y., Nishi, R., Hori, H., & Ueda, T. (2011). Characterization of cytarabine-resistant leukemic cell lines established from five different blood cell lineages using gene expression and proteomic analyses. International Journal of Oncology, 38, 911-919. https://doi.org/10.3892/ijo.2011.933
MLA
Negoro, E., Yamauchi, T., Urasaki, Y., Nishi, R., Hori, H., Ueda, T."Characterization of cytarabine-resistant leukemic cell lines established from five different blood cell lineages using gene expression and proteomic analyses". International Journal of Oncology 38.4 (2011): 911-919.
Chicago
Negoro, E., Yamauchi, T., Urasaki, Y., Nishi, R., Hori, H., Ueda, T."Characterization of cytarabine-resistant leukemic cell lines established from five different blood cell lineages using gene expression and proteomic analyses". International Journal of Oncology 38, no. 4 (2011): 911-919. https://doi.org/10.3892/ijo.2011.933