Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia.
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....
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182901&type=printable |
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| author | 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 |
| author_facet | 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 |
| author_sort | Alexander V Lavrov |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-aebeca0cfcc84482b693b260ee7cce6c |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-aebeca0cfcc84482b693b260ee7cce6c2025-08-20T02:46:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018290110.1371/journal.pone.0182901Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia.Alexander V LavrovOksana A UstaevaElmira P AdilgereevaSvetlana A SmirnikhinaEkaterina Y ChelyshevaOleg A ShukhovYuriy V ShatokhinSergey V MordanovAnna G TurkinaSergey I KutsevChronic 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182901&type=printable |
| spellingShingle | 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 Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia. PLoS ONE |
| title | Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia. |
| title_full | Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia. |
| title_fullStr | Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia. |
| title_full_unstemmed | Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia. |
| title_short | Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia. |
| title_sort | copy number variation analysis in cytochromes and glutathione s transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182901&type=printable |
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