Ozkan Busra, Altuner Torun Yasemin, Karakukcu Cigdem, Celik Binnaz
Department of Pediatrics, Beylikduzu Public Hospital, Istanbul 34500, Turkey.
The Faculty of Medicine, Department of Child Hematology and Oncology, Istinye University, Istanbul 34510, Turkey.
Children (Basel). 2024 Jan 31;11(2):176. doi: 10.3390/children11020176.
Acute lymphoblastic leukemias are the most common malignancies in childhood. Although its etiology is still unclear, it is thought that disorders in oxidative stress metabolism may contribute to leukemogenesis. Advanced glycation end products (AGEs) are formed as a result of the non-enzymatic binding of sugars to biomolecules. Oxidation reactions are triggered through AGE-Receptor (RAGE) interaction, resulting in the formation of reactive oxygen species. These can play crucial roles in cancer pathogenesis and leukemogenesis. It is thought that sRAGE (soluble RAGE) is the end product of glycation and circulates freely in the circulation by binding to RAGE ligands. We investigate novel leukemia biomarkers and focus on soluble RAGE (sRAGE) for acute lymphoblastic leukemia (ALL) diagnosis and prognosis. Thirty children (1-17 years) diagnosed with ALL were included in the study. Patients were divided into standard, medium, and high risk groups according to the Berlin-Frankfurt-Münster (BFM) treatment protocol. Patients were evaluated twice; at the time of diagnosis and at the sixth month of remission. sRAGE and blood parameters were compared with healthy controls ( = 30, 1-17 years). The sRAGE levels in ALL patients at diagnosis (138.7 ± 177.3 pg/mL) were found to be significantly higher than they were during the sixth month of remission (17.6 ± 21.1 pg/mL) and in healthy controls (22.2 ± 23.7 pg/mL). The cut-off value of the sRAGE level for the diagnosis of ALL was found to be 45 pg/mL in ROC analysis (sensitivity: 73.3%, specificity: 86.7%, AUC: 0.681). At the same time, the sRAGE level was found to be significantly higher in T-ALL patients (490.9 ± 236.9 pg/mL) than in B-ALL patients (84.5 ± 82.7 pg/mL). No significant difference was found in terms of the sRAGE level between standard (45.8± 33.1 pg/mL), medium (212 ± 222.1 pg/mL), and high (143.9 ± 111.5 pg/mL) risk group ALL patients classified according to the BFM protocol. Despite the fact that this was a small, single-center study, our findings highlight the potential use of sRAGE as a biomarker for diagnosing ALL and assessing response to treatment.
急性淋巴细胞白血病是儿童期最常见的恶性肿瘤。尽管其病因仍不清楚，但人们认为氧化应激代谢紊乱可能有助于白血病的发生。晚期糖基化终产物（AGEs）是糖与生物分子非酶结合的结果。通过AGE受体（RAGE）相互作用引发氧化反应，导致活性氧的形成。这些在癌症发病机制和白血病发生中可发挥关键作用。人们认为可溶性RAGE（sRAGE）是糖基化的终产物，通过与RAGE配体结合而在循环中自由循环。我们研究新型白血病生物标志物，并聚焦于可溶性RAGE（sRAGE）用于急性淋巴细胞白血病（ALL）的诊断和预后评估。30名诊断为ALL的儿童（1 - 17岁）纳入本研究。根据柏林 - 法兰克福 - 明斯特（BFM）治疗方案将患者分为标准、中危和高危组。对患者进行两次评估，分别在诊断时和缓解后第六个月。将sRAGE和血液参数与健康对照（n = 30，1 - 17岁）进行比较。发现ALL患者诊断时的sRAGE水平（138.7±177.3 pg/mL）显著高于缓解后第六个月（17.6±21.1 pg/mL）和健康对照（22.2±23.7 pg/mL）。在ROC分析中，ALL诊断的sRAGE水平截断值为45 pg/mL（敏感性：73.3%，特异性：86.7%，AUC：0.681）。同时，发现T - ALL患者的sRAGE水平（490.9±236.9 pg/mL）显著高于B - ALL患者（84.5±82.7 pg/mL）。根据BFM方案分类的标准（45.8±33.1 pg/mL）、中危（212±222.1 pg/mL）和高危（143.9±111.5 pg/mL）组ALL患者的sRAGE水平在差异无统计学意义。尽管这是一项小型单中心研究，但我们的发现突出了sRAGE作为诊断ALL和评估治疗反应生物标志物的潜在用途。
