Abstract

Pediatric acute myeloid leukemia (AML) is a devastating disease with a high risk of relapse. Current risk classification designates patients as high or low risk (LR) based on molecular features and therapy response. However, 30% of LR patients still suffer relapse, indicating a need for improvement in risk stratification. Cytokine levels, such as IL-6 and IL-10, have been shown to be prognostic in adult AML but have not been well studied in children. Previously, we reported elevated IL-6 levels in pediatric AML bone marrow to be associated with inferior prognosis. Here, we expanded our investigation to assess cytokine levels in diagnostic peripheral blood plasma (PBP) of pediatric AML patients and determined correlation with outcome. Diagnostic PBP was obtained from 80 patients with LR AML enrolled on the Children’s Oncology Group AAML1031 study and normal PBP from 11 controls. Cytokine levels were measured and correlation with clinical outcome was assessed. IL-6, TNFα, MIP-3a, and IL-1β were significantly higher in AML patients versus controls when corrected by the Bonferroni method. Furthermore, elevated TNFα and IL-10 were significantly associated with inferior outcomes. Our data demonstrate that in diagnostic PBP of LR pediatric AML patients, certain cytokine levels are elevated as compared to healthy controls and that elevated TNFα and IL-10 are associated with inferior outcomes, supporting the idea that an abnormal inflammatory state may predict poor outcomes. Studies are needed to determine the mechanisms by which these cytokines impact survival, and to further evaluate their use as prognostic biomarkers in pediatric AML.

 抽象的

儿童急性髓系白血病（AML）是一种毁灭性的疾病，复发风险很高。目前的风险分类根据分子特征和治疗反应将患者指定为高风险或低风险 (LR)。然而，30% 的 LR 患者仍会复发，表明需要改进风险分层。细胞因子水平，如 IL-6 和 IL-10，已被证明对成人 AML 具有预后作用，但尚未在儿童中得到充分研究。此前，我们报道儿童 AML 骨髓中 IL-6 水平升高与预后不良相关。在这里，我们扩大了研究范围，评估儿科 AML 患者诊断性外周血浆 (PBP) 中的细胞因子水平，并确定与结果的相关性。诊断性 PBP 是从参加儿童肿瘤组 AAML1031 研究的 80 名 LR AML 患者中获得的，而正常 PBP 是从 11 名对照中获得的。测量细胞因子水平并评估与临床结果的相关性。通过 Bonferroni 方法校正后，AML 患者的 IL-6、TNFα、MIP-3a 和 IL-1β 显着高于对照组。此外，TNFα 和 IL-10 升高与较差的预后显着相关。我们的数据表明，在 LR 儿科 AML 患者的诊断性 PBP 中，与健康对照相比，某些细胞因子水平升高，并且 TNFα 和 IL-10 升高与预后不良相关，这支持了异常炎症状态可能预示不良预后的观点。需要进行研究来确定这些细胞因子影响生存的机制，并进一步评估它们作为儿科 AML 预后生物标志物的用途。