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接受酪氨酸激酶抑制剂治疗的慢性髓性白血病患者的高敏 C 反应蛋白和循环内皮功能障碍生物标志物。

High sensitivity c-reactive protein and circulating biomarkers of endothelial dysfunction in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors.

机构信息

Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, Ted Rogers Program in Cardiotoxicity Prevention University Health Network, Toronto, Canada.

Division of Cardiology, Cardio-Oncology Program, McMaster University, Hamilton, Canada.

出版信息

Leuk Lymphoma. 2023 Dec;64(12):2008-2017. doi: 10.1080/10428194.2023.2242990. Epub 2023 Aug 9.

DOI:10.1080/10428194.2023.2242990
PMID:37554059
Abstract

Tyrosine kinase inhibitors (TKIs) have revolutionized the management of patients with chronic myelogenous leukemia (CML); however, they may cause cardiovascular (CV) toxicities. In this cross-sectional study, we explored whether high-sensitivity C-reactive protein (hsCRP) and novel markers of vascular dysfunction were associated with exposure to specific TKIs, in 262 CML patients. Hs-CRP level was not associated with CML disease activity or treatment with a specific TKI. Body mass index (OR: 1.15, 95% CI: 1.108-1.246;  < 0.001) and CML duration (OR: 1.004, 95% CI: 1.001-1.008;  = 0.024) were independently associated with higher hs-CRP. In exploratory analyses, novel endothelial-centric markers (e.g. ET-1 and VCAM-1) were differential across the various TKIs, particularly amongst nilotinib- and ponatinib-treated patients. While Levels of hs-CRP do not appear to be correlated with specific TKIs, circulating markers of vascular dysfunction were altered in patients treated with specific TKIs and should be explored as potential markers of TKI-associated CV risk.

摘要

酪氨酸激酶抑制剂 (TKI) 彻底改变了慢性髓细胞白血病 (CML) 患者的治疗方法;然而,它们可能会引起心血管 (CV) 毒性。在这项横断面研究中,我们探讨了 262 例 CML 患者中,高敏 C 反应蛋白 (hsCRP) 和血管功能障碍的新型标志物是否与特定 TKI 的暴露有关。hsCRP 水平与 CML 疾病活动度或特定 TKI 治疗无关。体重指数 (OR: 1.15, 95%CI: 1.108-1.246;  < 0.001) 和 CML 持续时间 (OR: 1.004, 95%CI: 1.001-1.008;  = 0.024) 与较高的 hsCRP 独立相关。在探索性分析中,新型内皮细胞中心标志物(例如 ET-1 和 VCAM-1)在各种 TKI 中存在差异,特别是在接受 nilotinib 和 ponatinib 治疗的患者中。虽然 hsCRP 水平似乎与特定 TKI 无关,但接受特定 TKI 治疗的患者的血管功能障碍的循环标志物发生了改变,应作为 TKI 相关 CV 风险的潜在标志物进行探索。

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