Cancers · 2025
Iron Dysregulation Signature in Pediatric Leukemia: In-Depth Biomarkers of Iron Metabolism Involving Matriptase-2 and Neogenin-1.
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Łęcka Monika, Słomka Artur, Albrecht Katarzyna, Romiszewski Michał, Styczyński Jan
Аннотация
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.
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.