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.

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生物医学领域的工程：分析与白血病治疗相关的内皮损伤背后的分子模式的跨行业方法


这项跨学科工作旨在展示基于将过程安全方法应用于生物医学领域的跨行业学习潜力，以专门了解与慢性粒细胞白血病治疗相关的血管并发症发展所涉及的分子过程。两种 BCR：：ABL1 酪氨酸激酶抑制剂尼罗替尼和伊马替尼目前用于治疗慢性粒细胞白血病，大多数接受治疗的患者实现了血液学和细胞遗传学的完全缓解，以及分子反应。然而，最近的长期随访研究表明，接受尼洛替尼治疗的患者心血管疾病的发病率增加。在这项研究中，提出了一种领结分析，以允许可视化导致内皮功能障碍和心血管风险的机制所涉及的分子模式。将临床观察、历史数据和专家意见与尼罗替尼对内皮细胞功能影响的体外评估相结合。实验结果表明，nilotinib 而不是 imatinib 诱导内皮细胞衰老和凋亡以及内皮标志物的调节。通过领结，了解与尼洛替尼相关的血管并发症发展所涉及的分子过程，以及屏障和升级因素的可视化和评估，可能有助于开发旨在预防心血管副作用的新方案。