Identification of target genes using gene expression profile of granulocytes from patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors

Abstract

Differential gene expression analysis by suppression subtractive hybridization with correlation to the metabolic pathways involved in chronic myeloid leukemia (CML) may provide a new insight into the pathogenesis of CML. Among the overexpressed genes found in CML at diagnosis are SEPT5, RUNX1, MIER1, KPNA6 and FLT3, while PAN3, TOB1 and ITCH were decreased when compared to healthy volunteers. Some genes were identified and involved in CML for the first time, including TOB1, which showed a low expression in patients with CML during tyrosine kinase inhibitor treatment with no complete cytogenetic response. In agreement, reduced expression of TOB1 was also observed in resistant patients with CML compared to responsive patients. This might be related to the deregulation of apoptosis and the signaling pathway leading to resistance. Most of the identified genes were related to the regulation of nuclear factor κB (NF-κB), AKT, interferon and interleukin-4 (IL-4) in healthy cells. The results of this study combined with literature data show specific gene pathways that might be explored as markers to assess the evolution and prognosis of CML as well as identify new therapeutic targets.

Keywords::

• Chronic myeloid leukemia
• suppression subtractive hybridization
• tyrosine kinase inhibitors

Acknowledgements

The authors wish to thank the Bioinformatics Group of the Genomics and Expression Laboratory (Department of Genetics and Evolution, Biology Institute, UNICAMP) for developing the computer program used to analyze the sequences, and the National Biosciences Laboratory, National Center for Research in Energy and Materials (CNPEM) for allowing the use of the software Ingenuity Pathway^®.

We appreciate the support of Prof. Dr. Fernando Araripe Gonçalves Torres (Institute of Biological Sciences, Department of Cell Biology, University of Brasília, DF, Brazil).

This study was funded by grants from the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP grants 2009/53388-0).

The authors also wish to thank CNPq, FAPESP, and INCT-Sangue for financial support.

Potential conflict of interest:

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