Open Access

Investigating critical genes and gene interaction networks that mediate cyclophosphamide sensitivity in chronic myelogenous leukemia

  • Authors:
    • Xiao He
    • Yuying Deng
    • Wei Yue
  • View Affiliations

  • Published online on: May 26, 2017     https://doi.org/10.3892/mmr.2017.6636
  • Pages: 523-532
  • Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Drug resistance is an obstacle in the treatment of chronic myelogenous leukemia (CML), and is a common reason for treatment failure or disease progression. However, the underlying mechanisms of cyclophosphamide resistance remain poorly defined. In the present study, microarray data concerning cyclophosphamide‑sensitive and ‑resistant chronic myelogenous leukemia cell lines were analyzed. A total of 258 differentially‑expressed genes (DEGs) were identified between these two groups, from which 139 DEGs were upregulated and 119 were downregulated. Several candidate genes that were associated with cyclophosphamide resistance were also identified. These DEGs were subsequently classified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis. A total of 487 biological processes and 17 KEGG pathways were revealed to be enriched. Furthermore, an interaction network was established to identify the core genes that regulated cyclophosphamide resistance. Signal transducer and activator of transcription 5A (STAT5A), FYN proto‑oncogene, Src family tyrosine kinase and spleen associated tyrosine kinase were revealed to be the hub genes in multiple enriched biological processes and signaling pathways, indicating that these were involved in mediating cyclophosphamide sensitivity in CML cells. The expression levels of 5 DEGs were also confirmed in two human CML cell lines (K‑562 and KU812) by reverse transcription‑quantitative polymerase chain reaction. Furthermore, selective knockdown of STAT5A and S100 calcium binding protein A4 (S100A4) recovered cyclophosphamide sensitivity in K‑562 cells, suggesting their involvement in drug resistance. The present study identified several potential genes and pathways contributing to cyclophosphamide resistance, and confirmed the involvement of STAT5A and S100A4 in drug resistance. These results enable improved understanding of the mechanisms underlying drug resistance in CML cells.
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July-2017
Volume 16 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
He X, Deng Y and Yue W: Investigating critical genes and gene interaction networks that mediate cyclophosphamide sensitivity in chronic myelogenous leukemia. Mol Med Rep 16: 523-532, 2017
APA
He, X., Deng, Y., & Yue, W. (2017). Investigating critical genes and gene interaction networks that mediate cyclophosphamide sensitivity in chronic myelogenous leukemia. Molecular Medicine Reports, 16, 523-532. https://doi.org/10.3892/mmr.2017.6636
MLA
He, X., Deng, Y., Yue, W."Investigating critical genes and gene interaction networks that mediate cyclophosphamide sensitivity in chronic myelogenous leukemia". Molecular Medicine Reports 16.1 (2017): 523-532.
Chicago
He, X., Deng, Y., Yue, W."Investigating critical genes and gene interaction networks that mediate cyclophosphamide sensitivity in chronic myelogenous leukemia". Molecular Medicine Reports 16, no. 1 (2017): 523-532. https://doi.org/10.3892/mmr.2017.6636