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Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients
Several reports described an increased risk of cardiovascular (CV) events, mainly atherothrombotic, in Chronic Myeloid Leukemia (CML) patients receiving nilotinib. However, the underlying mechanism remains elusive. The objective of the current cross-sectional retrospective study is to address a pote...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342164/ https://www.ncbi.nlm.nih.gov/pubmed/27527867 http://dx.doi.org/10.18632/oncotarget.11100 |
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author | Bocchia, Monica Galimberti, Sara Aprile, Lara Sicuranza, Anna Gozzini, Antonella Santilli, Francesca Abruzzese, Elisabetta Baratè, Claudia Scappini, Barbara Fontanelli, Giulia Trawinska, Monika Malgorzata Defina, Marzia Gozzetti, Alessandro Bosi, Alberto Petrini, Mario Puccetti, Luca |
author_facet | Bocchia, Monica Galimberti, Sara Aprile, Lara Sicuranza, Anna Gozzini, Antonella Santilli, Francesca Abruzzese, Elisabetta Baratè, Claudia Scappini, Barbara Fontanelli, Giulia Trawinska, Monika Malgorzata Defina, Marzia Gozzetti, Alessandro Bosi, Alberto Petrini, Mario Puccetti, Luca |
author_sort | Bocchia, Monica |
collection | PubMed |
description | Several reports described an increased risk of cardiovascular (CV) events, mainly atherothrombotic, in Chronic Myeloid Leukemia (CML) patients receiving nilotinib. However, the underlying mechanism remains elusive. The objective of the current cross-sectional retrospective study is to address a potential correlation between Tyrosine Kinase Inhibitors (TKIs) treatment and CV events. One hundred and 10 chronic phase CML patients in complete cytogenetic response during nilotinib or imatinib, were screened for CV events and evaluated for: traditional CV risk factors, pro/anti-inflammatory biochemical parameters and detrimental ORL1 gene polymorphisms (encoding for altered oxidized LDL receptor-1). Multivariate analysis of the whole cohort showed that the cluster of co-existing nilotinib treatment, dyslipidaemia and G allele of LOX-1 polymorphism was the only significant finding associated with CV events. Furthermore, multivariate analysis according to TKI treatment confirmed IVS4-14 G/G LOX-1 polymorphism as the strongest predictive factor for a higher incidence of CV events in nilotinib patients. Biochemical assessment showed an unbalanced pro-inflammatory cytokines network in nilotinib vs imatinib patients. Surprisingly, pre-existing traditional CV risk factors were not always predictive of CV events. We believe that in nilotinib patients an induced “inflammatory/oxidative status”, together with a genetic pro-atherothrombotic predisposition, may favour the increased incidence of CV events. Prospective studies focused on this issue are ongoing. |
format | Online Article Text |
id | pubmed-5342164 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53421642017-03-24 Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients Bocchia, Monica Galimberti, Sara Aprile, Lara Sicuranza, Anna Gozzini, Antonella Santilli, Francesca Abruzzese, Elisabetta Baratè, Claudia Scappini, Barbara Fontanelli, Giulia Trawinska, Monika Malgorzata Defina, Marzia Gozzetti, Alessandro Bosi, Alberto Petrini, Mario Puccetti, Luca Oncotarget Clinical Research Paper Several reports described an increased risk of cardiovascular (CV) events, mainly atherothrombotic, in Chronic Myeloid Leukemia (CML) patients receiving nilotinib. However, the underlying mechanism remains elusive. The objective of the current cross-sectional retrospective study is to address a potential correlation between Tyrosine Kinase Inhibitors (TKIs) treatment and CV events. One hundred and 10 chronic phase CML patients in complete cytogenetic response during nilotinib or imatinib, were screened for CV events and evaluated for: traditional CV risk factors, pro/anti-inflammatory biochemical parameters and detrimental ORL1 gene polymorphisms (encoding for altered oxidized LDL receptor-1). Multivariate analysis of the whole cohort showed that the cluster of co-existing nilotinib treatment, dyslipidaemia and G allele of LOX-1 polymorphism was the only significant finding associated with CV events. Furthermore, multivariate analysis according to TKI treatment confirmed IVS4-14 G/G LOX-1 polymorphism as the strongest predictive factor for a higher incidence of CV events in nilotinib patients. Biochemical assessment showed an unbalanced pro-inflammatory cytokines network in nilotinib vs imatinib patients. Surprisingly, pre-existing traditional CV risk factors were not always predictive of CV events. We believe that in nilotinib patients an induced “inflammatory/oxidative status”, together with a genetic pro-atherothrombotic predisposition, may favour the increased incidence of CV events. Prospective studies focused on this issue are ongoing. Impact Journals LLC 2016-08-05 /pmc/articles/PMC5342164/ /pubmed/27527867 http://dx.doi.org/10.18632/oncotarget.11100 Text en Copyright: © 2016 Bocchia et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Clinical Research Paper Bocchia, Monica Galimberti, Sara Aprile, Lara Sicuranza, Anna Gozzini, Antonella Santilli, Francesca Abruzzese, Elisabetta Baratè, Claudia Scappini, Barbara Fontanelli, Giulia Trawinska, Monika Malgorzata Defina, Marzia Gozzetti, Alessandro Bosi, Alberto Petrini, Mario Puccetti, Luca Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients |
title | Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients |
title_full | Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients |
title_fullStr | Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients |
title_full_unstemmed | Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients |
title_short | Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients |
title_sort | genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients |
topic | Clinical Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342164/ https://www.ncbi.nlm.nih.gov/pubmed/27527867 http://dx.doi.org/10.18632/oncotarget.11100 |
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