# The Imbalanced Patterns and Clinical Significance of Cytokines in Acute Myeloid Leukemia Microenvironment

## TL;DR

This study explores how imbalanced cytokine patterns in the AML microenvironment are linked to poor patient outcomes and identifies CCL3, CCL4, and CXCL10 as potential biomarkers for prognosis.

## Contribution

The study identifies CCL3, CCL4, and CXCL10 as cytokines independently associated with poor AML prognosis, regardless of patient characteristics.

## Key findings

- AML mice and patients showed imbalanced cytokine patterns.
- High levels of CCL3, CCL4, and CXCL10 correlated with poor AML patient survival.
- Treg cells and B cells may influence CCL3 and CXCL10 levels in the AML microenvironment.

## Abstract

Acute myeloid leukemia (AML) is known for its unfavorable prognosis, prompting research efforts of cytokines in the microenvironment to explore new therapeutic targets. Here, we investigated the complex cytokine networks in both AML mice and AML patients to reveal the role of cytokines in AML pathogenesis.

As a basis for further studies on human, the patterns of cytokines were detected in AML mice by cytokine array panel, and the patterns of cytokines were detected in AML patients by Luminex liquid suspension chip and ELISA. Leukocyte subpopulations in human were analyzed by flow cytometry. Additionally, the associations of cytokine levels with the outcome of AML patients were analyzed by Cox regression analysis, the overall survival curve was assessed by Kaplan‐Meier method. Furthermore, Pearson correlation analysis was used for the correlation analysis of continuous variables.

The imbalanced patterns of cytokines were observed in AML mice. Furthermore, higher levels of CCL3, CCL4 and CXCL10, independent of sex, age, FAB phenotype, patient status and risk molecular, were associated with the poor outcome of AML patients recruited in our study by Cox regression analysis. Additionally, the survival analysis demonstrated that the CCL3high group had a shorter overall survival than the CCL3low group, and a similar result was observed in the analysis of CXCL10. The correlation analysis revealed that Treg cells may be related to the increase of CCL3, while B cell may be associated with for the changes of CXCL10 in AML microenvironment.

The imbalanced patterns of cytokines were observed in both AML mice and AML patients. Interestingly, 3 cytokines (CCL3, CCL4 and CXCL10) were related to the outcome of AML patients, suggesting they are valuable for AML prognosis. Furthermore, the change of leukocyte subpopulations, either as causes or as consequences, may partially account for the change of cytokines in AML condition.

Higher levels of CCL3, CCL4 and CXCL10, independent of sex, age, FAB phenotype, patient status and risk molecular, were associated with the poor outcome of AML patients.