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

Autor:	Lavrov AV; Laboratory of Mutagenesis, Federal State Budgetary Institution Research Centre for Medical Genetics, Moscow, Russian Federation.; Department of Molecular and Cellular Genetics, State Budgetary Educational Institution of Higher Professional Education Russian National Research Medical University named after N.I. Pirogov of Ministry of Health of the Russian Federation, Moscow, Russian Federation., Ustaeva OA; Laboratory of Medical Genetics, The Rostov State Medical University, Rostov-on-Don, Russian Federation., Adilgereeva EP; Laboratory of Mutagenesis, Federal State Budgetary Institution Research Centre for Medical Genetics, Moscow, Russian Federation., Smirnikhina SA; Laboratory of Mutagenesis, Federal State Budgetary Institution Research Centre for Medical Genetics, Moscow, Russian Federation., Chelysheva EY; Scientific and Advisory Department of Chemotherapy of Myeloproliferative disorders, Federal State-Funded Institution National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation., Shukhov OA; Scientific and Advisory Department of Chemotherapy of Myeloproliferative disorders, Federal State-Funded Institution National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation., Shatokhin YV; Laboratory of Medical Genetics, The Rostov State Medical University, Rostov-on-Don, Russian Federation., Mordanov SV; Laboratory of Medical Genetics, The Rostov State Medical University, Rostov-on-Don, Russian Federation., Turkina AG; Scientific and Advisory Department of Chemotherapy of Myeloproliferative disorders, Federal State-Funded Institution National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation., Kutsev SI; Laboratory of Mutagenesis, Federal State Budgetary Institution Research Centre for Medical Genetics, Moscow, Russian Federation.; Department of Molecular and Cellular Genetics, State Budgetary Educational Institution of Higher Professional Education Russian National Research Medical University named after N.I. Pirogov of Ministry of Health of the Russian Federation, Moscow, Russian Federation.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2017 Sep 13; Vol. 12 (9), pp. e0182901. Date of Electronic Publication: 2017 Sep 13 (Print Publication: 2017).
DOI:	10.1371/journal.pone.0182901
Abstrakt:	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.
Databáze:	MEDLINE
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