Engineering for Biomedical Sector: A Cross-Industry Approach for the Analysis of Molecular Patterns behind Endothelial Damage Related to Leukemia Therapy

This transdisciplinary work aims to demonstrate cross-industry learning potential based on the application of a process safety approach to the biomedical sector for specifically understanding the molecular processes involved in the development of vascular complications associated with therapies for chronic myeloid leukemia. Two BCR::ABL1 tyrosine kinase inhibitors, nilotinib and imatinib, are currently used in the treatment of chronic myeloid leukemia with the majority of treated patients achieving complete hematological and cytogenetic remission, as well as molecular response. Nevertheless, recent long-term follow-up studies have shown an increased incidence of cardiovascular disease in patients treated with nilotinib. In this study, a bow-tie analysis is proposed to allow the visualization of molecular patterns involved in the mechanism leading to endothelial dysfunction and cardiovascular risks. Clinical observations, historical data, and expert opinions were combined with an in vitro evaluation of the effects of nilotinib on endothelial cell function. Experimental results showed that nilotinib, but not imatinib, induces both senescence and apoptosis in endothelial cells along with the modulation of endothelial markers. Through the bow-tie, understanding the molecular processes involved in the development of vascular complications associated with nilotinib, as well as the visualization and assessment of barriers and escalation factors, could contribute to the development of novel protocols aimed at preventing cardiovascular side effects.