Clinical Research Papers:

Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients

Monica Bocchia _, Sara Galimberti, Lara Aprile, Anna Sicuranza, Antonella Gozzini, Francesca Santilli, Elisabetta Abruzzese, Claudia Baratè, Barbara Scappini, Giulia Fontanelli, Monika Malgorzata Trawinska, Marzia Defina, Alessandro Gozzetti, Alberto Bosi, Mario Petrini and Luca Puccetti

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Oncotarget. 2016; 7:72311-72321. https://doi.org/10.18632/oncotarget.11100

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Monica Bocchia1, Sara Galimberti2, Lara Aprile1, Anna Sicuranza1, Antonella Gozzini3, Francesca Santilli4, Elisabetta Abruzzese5, Claudia Baratè2, Barbara Scappini3, Giulia Fontanelli2, Monika Malgorzata Trawinska5, Marzia Defina1, Alessandro Gozzetti1, Alberto Bosi3, Mario Petrini2 and Luca Puccetti1

1 Department of Hematology, University of Siena, Azienda Ospedaliera Universitaria Senese, Siena, Italy

2 Department of Clinical and Experimental Medicine, U.O. Hematology, University of Pisa, Pisa, Italy

3 Functional Unit of Hematology, University of Florence, Florence, Italy

4 Department of Medicine and Aging, University of Chieti, Chieti, Italy

5 Hematology Unit, S. Eugenio Hospital, Tor Vergata University, Rome, Italy


Monica Bocchia, email:

Keywords: PAOD, TKI, CML, inflammation, atherothrombotic risk

Received: March15, 2016 Accepted: July 18, 2016 Published: August 05, 2016


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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