PLoS ONE (Jan 2017)

Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia.

  • Alexander V Lavrov,
  • Oksana A Ustaeva,
  • Elmira P Adilgereeva,
  • Svetlana A Smirnikhina,
  • Ekaterina Y Chelysheva,
  • Oleg A Shukhov,
  • Yuriy V Shatokhin,
  • Sergey V Mordanov,
  • Anna G Turkina,
  • Sergey I Kutsev

DOI
https://doi.org/10.1371/journal.pone.0182901
Journal volume & issue
Vol. 12, no. 9
p. e0182901

Abstract

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Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of BCR/ABL fusion gene in leukemic cells, which promotes uncontrolled cell proliferation. Up to 20% of CML patients show primary resistance or non-optimal response to tyrosine kinase inhibitor (TKI) therapy. We investigated the association between copy number variation (CNV) in glutathione S-transferases (GST) and cytochromes (CYP) and the response rate to TKI. We enrolled 47 patients with CML: 31 with an optimal response and 16 with failure at 6 months in accordance with European LeukemiaNet 2013 recommendations. CNV detection was performed using SALSA MLPA P128-C1 Cytochrome P450 probe mix. Patients with optimal response and with failure of TKI therapy showed different frequencies of wild type and mutated CYPs and GST (p<0.0013). Validation in the group of 15 patients proved high prognostic value (p = 0.02): positive and negative predictive value 83% and 78%; sensitivity and specificity 71% and 88%. Wild type genotypes of CYP and GST associate with a worse response to TKI treatment in CML patients. This test can be recommended for further clinical trials.