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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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.
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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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