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脑脊液白细胞介素-6是成人急性髓系白血病中枢神经系统受累的潜在诊断生物标志物。

Cerebrospinal fluid interleukin-6 is a potential diagnostic biomarker for central nervous system involvement in adult acute myeloid leukemia.

作者信息

Gu Jiayan, Huang Xin, Zhang Yi, Bao Chenhui, Zhou Ziyang, Tong Hongyan, Jin Jie

机构信息

Institute of Hematology, Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Zhejiang, Hangzhou, China.

出版信息

Front Oncol. 2022 Dec 1;12:1013781. doi: 10.3389/fonc.2022.1013781. eCollection 2022.

Abstract

OBJECTIVE

We evaluated the correlation between cerebrospinal fluid (CSF) cytokine levels and central nervous system (CNS) involvement in adult acute myeloid leukemia (AML).

METHODS

The study sample consisted of 90 patients diagnosed with AML and 20 with unrelated CNS involvement. The AML group was divided into two sub-groups: those with (CNS+, n=30) and without CNS involvement (CNS-, n=60). We used a cytometric bead assay to measure CSF interleukin (IL)-2, IL-4, IL-6, and IL-10, tumor necrosis factor-α, interferon-γ, and IL-17A. We used receiver operating characteristic curves to evaluate the ability of CSF cytokine levels to identify CNS involvement in adult AML.

RESULTS

CSF IL-6 levels were significantly higher in CNS+adult AML patients and positively correlated with the lactate dehydrogenase levels (r=0.738, p<0.001) and white blood cell (WBC) count (r=0.455, p=0.012) in the blood, and the protein (r=0.686, p<0.001) as well as WBC count in the CSF (r=0.427, p=0.019). Using a CSF IL-6 cut-off value of 8.27 pg/ml yielded a diagnostic sensitivity and specificity was 80.00% and 88.46%, respectively (AUC, 0.8923; 95% CI, 0.8168-0.9678). After treating a subset of tested patients, their CSF IL-6 levels decreased. Consequently, the elevated CSF IL-6 levels remaining in CNS+ adult AML patients post-treatment were associated with disease progression.

CONCLUSION

CSF IL-6 is a promising marker for the diagnosis of adult AML with CNS involvement and a crucial dynamic indicator for therapeutic response.

摘要

目的

我们评估了脑脊液(CSF)细胞因子水平与成人急性髓系白血病(AML)中枢神经系统(CNS)受累之间的相关性。

方法

研究样本包括90例诊断为AML的患者和20例伴有无关CNS受累的患者。AML组分为两个亚组:有CNS受累的患者(CNS+,n = 30)和无CNS受累的患者(CNS-,n = 60)。我们使用细胞计数珠分析法测量CSF白细胞介素(IL)-2、IL-4、IL-6和IL-10、肿瘤坏死因子-α、干扰素-γ以及IL-17A。我们使用受试者工作特征曲线来评估CSF细胞因子水平识别成人AML中CNS受累的能力。

结果

CNS+成人AML患者的CSF IL-6水平显著更高,且与血液中的乳酸脱氢酶水平(r = 0.738,p < 0.001)、白细胞(WBC)计数(r = 0.455,p = 0.012)以及CSF中的蛋白(r = 0.686,p < 0.001)和WBC计数(r = 0.427,p = 0.019)呈正相关。使用CSF IL-6临界值8.27 pg/ml时,诊断敏感性和特异性分别为80.00%和88.46%(曲线下面积,0.8923;95%可信区间,0.8168 - 0.9678)。在治疗一部分受试患者后,他们的CSF IL-6水平下降。因此,治疗后CNS+成人AML患者中仍升高的CSF IL-6水平与疾病进展相关。

结论

CSF IL-6是诊断伴有CNS受累的成人AML的一个有前景的标志物,也是治疗反应的一个关键动态指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/344c/9751393/e80db83a697c/fonc-12-1013781-g001.jpg

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