Background: Acute leukemia (AL) is the most prevalent pediatric malignancy and is frequently associated with systemic iron dysregulation, often leading to iron overload. This study aimed to characterize the regulatory mechanisms of iron metabolism in children with AL, considering treatment stages and associated clinical parameters. Methods: A total of 149 children were stratified into four groups: newly diagnosed AL (n= 43), patients post-chemotherapy (n= 55), patients following hematopoietic cell transplantation (HCT;n= 32), and healthy controls (n= 19). Serum concentrations of matriptase-2 (TMPRSS6), neogenin-1 (NEO1), and soluble hemojuvelin (sHJV) were quantified using ELISA. Results: Compared to healthy children, significantly higher serum concentrations of TMPRSS6 and NEO1 were found in patients post-chemotherapy and post-HCT, while sHJV levels were markedly decreased. Higher TMPRSS6 and NEO1 levels and lower sHJV were associated with increased ferritin levels and greater numbers of transfused packed red blood cell (PRBC) units. sHJV negatively correlated with TMPRSS6, NEO1, ferritin, C-reactive protein (CRP), and PRBC transfusions. TMPRSS6 and NEO1 showed a positive correlation. Among the analyzed biomarkers, Kaplan–Meier analysis revealed no statistically significant associations with overall survival (OS) or event-free survival (EFS) within the chemotherapy and HCT subgroups. Conclusions: AL in pediatric patients is associated with profound disruptions of systemic iron homeostasis. Our investigation identified notable perturbations in TMPRSS6, NEO1, and sHJV, suggesting that these proteins could contribute mechanistically to the pathophysiological alterations underlying iron dysregulation observed in pediatric AL.
背景：急性白血病（AL）是儿童中最常见的恶性肿瘤，常伴随全身性铁代谢紊乱，并易导致铁过载。本研究旨在探讨儿童AL患者铁代谢的调控机制，并分析其与治疗阶段及相关临床参数的关系。方法：共纳入149名儿童，分为四组：新诊断AL组（n=43）、化疗后组（n=55）、造血细胞移植后组（HCT；n=32）及健康对照组（n=19）。采用酶联免疫吸附法测定血清中基质蛋白酶-2（TMPRSS6）、神经生成素-1（NEO1）及可溶性血幼素（sHJV）的浓度。结果：与健康儿童相比，化疗后及HCT后患者的血清TMPRSS6和NEO1浓度显著升高，而sHJV水平明显降低。较高的TMPRSS6和NEO1水平及较低的sHJV水平与较高的铁蛋白水平及更多的浓缩红细胞输注单位数相关。sHJV与TMPRSS6、NEO1、铁蛋白、C反应蛋白及浓缩红细胞输注量呈负相关，而TMPRSS6与NEO1呈正相关。在化疗及HCT亚组中，Kaplan-Meier分析显示所分析的生物标志物与总生存期或无事件生存期均无统计学显著关联。结论：儿童AL患者存在严重的全身铁稳态失衡。本研究发现TMPRSS6、NEO1和sHJV存在显著异常，提示这些蛋白可能在儿童AL铁代谢紊乱的病理生理改变中发挥机制性作用。
肿瘤(癌症)患者之家