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

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

Jiayan Gu  1   2 , Xin Huang  1   2 , Yi Zhang  1   2 , Chenhui Bao  1   2 , Ziyang Zhou  1   2 , Hongyan Tong  1   2 , Jie Jin  1   2
Affiliations

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

Jiayan Gu et al. Front Oncol. .

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.

Keywords: acute myeloid leukemia; biomarker; central nervous system; cerebrospinal fluid; interleukin-6.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Cytokine profiles in adult AML patients with and without CNS involvement (AML with CNS+ and CNS-) and other CNS diseases. AML, acute myeloid leukemia; CNS, central nervous system.
Figure 2
Figure 2
Correlation between the CSF IL-6 level and blood WBC count/CSF WBC count/blood LDH/CSF protein levels in adult AML patients. CSF, cerebrospinal fluid; IL, interleukin; LDH, lactate dehydrogenase; AML, acute myeloid leukemia.
Figure 3
Figure 3
Receiver-operator characteristic (ROC) curves of the CSF IL-6. IL-6: sensitivity 80.00% and specificity 88.46% at 8.27 pg/ml (AUC, 0.8923; 95% CI, 0.8168–0.9678). AUC, area under the curve; CI, confidence interval.
Figure 4
Figure 4
Changes in the CSF IL-6 level between AML with CNS involvement during diagnosis and post-treatment (n=16).
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