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Molecular study of ABCB1 gene and its correlation with imatinib response in chronic myeloid leukemia

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Abstract

Purpose

The introduction and success of imatinib mesylate have become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, despite its high efficiency, resistance to imatinib has emerged as a significant problem, which may in part be caused by pharmacogenetic variability. Three single-nucleotide polymorphisms (C1236T, G2677T/A, C3435T) and/or mRNA expression changes of ABCB1 gene were demonstrated to be associated with inter-individual variability of imatinib response in CML patients. In this study, we aimed to examine whether genetic variations and/or altered expression of ABCB1 gene may influence response to imatinib.

Methods

Sixty nine CML Tunisian patients, undergoing imatinib therapy, were enrolled in this study. These were divided into two groups: responders and non-responders to imatinib. The relative transcript expression levels of ABCB1 gene and the distribution of allele and genotype frequency of ABCB1 SNPs were compared between these two categories of patients. Linkage disequilibrium tests and haplotypes analysis were also studied.

Results

Our results showed that the mRNA expression level of ABCB1 gene did not differ significantly between the two categories of patients. In addition, results obtained from ABCB1 polymorphisms study and their correlation with imatinib response showed that the optimal response rate to imatinib did not differ significantly between C1236T, G2677T/A or C3435T genotypes. However, haplotype analysis showed that the 1236C–2677A–3435C haplotype was observed only in imatinib non-responders’ patients suggesting that CAC haplotype was linked to higher risk of imatinib resistance.

Conclusion

Furthermore, analyses of ABCB1 haplotypes should be taken into account to study the relationship between ABCB1 genotypes and imatinib efficacy.

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Acknowledgements

We wish to thank all the staff members of the Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis (LR11 IPT07). This work was supported by the Ministry of Higher Education and Scientific Research in Tunisia.

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Authors and Affiliations

  1. Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, 13 Place Pasteur, BP 74, 1002, Belvedere, Tunis, Tunisia

    Islem Ben Hassine, Hanene Gharbi, Ismail Soltani, Hind Ben Hadj Othman, Ahlem Farrah, Hassiba Amouri, Mouheb Teber, Ines Safra, Salem Abbes & Samia Menif

  2. Faculte de Medecine de Tunis, Universite de Tunis El Manar, Tunis, Tunisia

    Hela Ghedira, Yosra Ben Youssef, Ines Safra & Samia Menif

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  1. Islem Ben Hassine
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  2. Hanene Gharbi
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  3. Ismail Soltani
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Correspondence to Islem Ben Hassine.

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Ben Hassine, I., Gharbi, H., Soltani, I. et al. Molecular study of ABCB1 gene and its correlation with imatinib response in chronic myeloid leukemia. Cancer Chemother Pharmacol 80, 829–839 (2017). https://doi.org/10.1007/s00280-017-3424-4

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