Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, China.
Pediatr Res. 2021 Apr;89(5):1245-1252. doi: 10.1038/s41390-020-1049-5. Epub 2020 Jul 7.
We investigated whether plasma high-sensitivity cardiac troponin T (hs-cTnT) and circulating heart-associated microRNA (miRs) are increased in children with leukaemias during anthracycline-based chemotherapeutic treatment.
In vitro human pluripotent stem cell (hPSC)-derived cardiomyocyte model showed that miR-1, miR-133a, miR-208a, miR-208b, and miR-499 are released from cells into culture medium in a time- and dose-dependent manner on doxorubicin exposure. Left ventricular (LV) myocardial deformation and circulating heart-associated miRs and plasma hs-cTnT during and after completion of chemotherapy were determined in 40 children with newly diagnosed acute leukaemia.
Significant reduction of LV global longitudinal strain and strain rates were found within 1 week after completion of anthracycline therapy in the induction phase of treatment (all p < 0.05). Hs-cTnT level peaked and miR-1 increased significantly at this time point. Log-transformed hs-cTnT correlated negatively with LV global systolic longitudinal strain (r = -0.38, p < 0.001). Receiver operating characteristic analysis revealed that area under the curve for changes in plasma hs-cTnT from baseline and plasma miR-1 levels in detecting a reduction in ≥20% of global longitudinal strain were respectively 0.62 (95% CI 0.38-0.87) and 0.62 (95% CI 0.40-0.84).
Plasma hs-cTnT and circulating miR-1 may be useful markers of myocardial damage during chemotherapy in children with leukaemias.
Heart-associated miRNAs including miR-1, miR-133a, miR-208a, miR-208b,and miR-499 were increased in the culture medium upon exposure of hPSC-derived cardiomyocytes to doxorubicin. Only miR-1 increased significantly during anthracycline-based therapy in paediatric leukaemic patients. In paediatric leukaemic patients, plasma hs-cTnT and circulating level of miR-1 showed the most significant increase within 1 week after completion of anthracycline therapy in the induction treatment phase. The study provides the first evidence of progressive increase in circulating miR-1 and plasma hs-cTnT levels during the course of anthracycline-based therapy in children with leukaemias, with hs-cTnT level also associated with changes in LV myocardial deformation.
我们研究了在接受基于蒽环类药物的化疗治疗期间，白血病患儿的血浆高敏心肌肌钙蛋白 T（hs-cTnT）和循环心脏相关 microRNA（miRs）是否增加。
体外人多能干细胞（hPSC）衍生的心肌细胞模型显示，miR-1、miR-133a、miR-208a、miR-208b 和 miR-499 在阿霉素暴露时以时间和剂量依赖性方式从细胞释放到培养基中。在 40 名新诊断为急性白血病的儿童中，测定化疗期间和完成后左心室（LV）心肌变形以及循环心脏相关 miRs 和血浆 hs-cTnT。
在诱导治疗阶段的化疗完成后 1 周内，发现 LV 整体纵向应变和应变率明显下降（均 p<0.05）。hs-cTnT 水平在此时显著升高，miR-1 也明显升高。经对数转换的 hs-cTnT 与 LV 整体收缩纵向应变呈负相关（r=-0.38，p<0.001）。受试者工作特征分析显示，从基线开始血浆 hs-cTnT 和血浆 miR-1 水平变化的曲线下面积分别为 0.62（95%CI 0.38-0.87）和 0.62（95%CI 0.40-0.84），用于检测整体纵向应变降低≥20%。
血浆 hs-cTnT 和循环 miR-1 可能是白血病患儿化疗期间心肌损伤的有用标志物。
hPSC 衍生的心肌细胞暴露于阿霉素后，培养基中包括 miR-1、miR-133a、miR-208a、miR-208b 和 miR-499 在内的心脏相关 miRNA 增加。在接受基于蒽环类药物的治疗的儿科白血病患者中，只有 miR-1 显著增加。在儿科白血病患者中，在诱导治疗阶段化疗完成后 1 周内，血浆 hs-cTnT 和循环 miR-1 水平显著增加。该研究首次提供了在白血病患儿接受蒽环类药物治疗过程中循环 miR-1 和血浆 hs-cTnT 水平逐渐增加的证据，hs-cTnT 水平也与 LV 心肌变形的变化相关。
