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High CX3CR1 expression predicts poor prognosis in paediatric acute myeloid leukaemia undergoing hyperleukocytosis
1Department of Hematology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Insights
Elevated CX3CR1 expression is linked to poor prognosis in childhood acute myeloid leukemia (AML) with hyperleukocytosis. This gene may also be a target for immunotherapy in these pediatric AML patients.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Childhood acute myeloid leukemia (AML) with hyperleukocytosis presents a significant challenge due to poor prognosis and high early mortality.
- Identifying reliable prognostic indicators is crucial for improving outcomes in pediatric AML patients with hyperleukocytosis.
Purpose of the Study:
- To identify novel prognostic biomarkers for pediatric AML patients with hyperleukocytosis.
- To explore the potential of CX3CR1 as a therapeutic target in this patient group.
Main Methods:
- Differential gene expression analysis was performed on data from the TARGET database to identify genes associated with hyperleukocytosis in pediatric AML.
- Univariate Cox regression, Cytoscape, and Kaplan-Meier survival analysis were used to identify and validate target genes.
- Functional network and immune-related activity analyses were conducted using multiple bioinformatics databases.
Main Results:
- 1229 differentially expressed genes (DEGs) were identified between hyperleukocytosis and non-hyperleukocytosis groups in pediatric AML.
- CX3CR1 was identified as a significant target gene and an independent prognostic predictor, with 495 DEGs linked to overall survival.
- CX3CR1 expression correlated with immune cell infiltration and modulated immune response pathways, particularly involving monocytes, NK cells, and CD8 T cells.
Conclusions:
- Elevated CX3CR1 expression serves as an adverse prognostic indicator in pediatric AML with hyperleukocytosis.
- CX3CR1 presents a potential immunotherapeutic target for treating childhood AML complicated by hyperleukocytosis.
Introduction:
Paediatric AML patients with hyperleukocytosis have a poor prognosis and higher early mortality. Therefore, more studies are needed to explore relevant prognostic indicators and develop effective prevention strategies for this type of childhood AML.
Methods:
All original data were obtained from the TARGET database. First, we explored meaningful differentially expressed genes (DEGs) between the hyperleukocytosis group and the non-hyperleukocytosis group. Next, we screened and identified valuable target genes using univariate Cox regression, Cytoscape software, and Kaplan-Meier survival curves. Finally, the coexpressed genes, functional networks, and immune-related activities associated with the target gene were deeply analysed by the GeneMANIA, LinkedOmics, GEPIA2021, TISIDB, and GSCA databases.
Results:
We selected 1229 DEGs between the hyperleukocytosis group and the non-hyperleukocytosis group in paediatric AML patients. Among them, 495 DEGs were significantly linked with the overall survival of paediatric AML patients. Further, we discovered that CX3CR1 was a promising target gene. Meanwhile, we identified CX3CR1 as an independent prognostic predictor. Besides, we showed that CX3CR1 had strong physical interactions with CX3CL1. Additionally, functional network analysis suggested that CX3CR1 and its coexpressed genes modulated immune response pathways. Subsequent analysis found that immune cells with a high median value of CX3CR1 were monocytes, resting NK cells and CD8 T cells. Finally, we observed that CX3CR1 expression correlated with infiltrating levels of immune cells and immune signatures.
Conclusion:
Elevated CX3CR1 expression may be an adverse prognostic indicator in paediatric AML patients undergoing hyperleukocytosis. Moreover, CX3CR1 may serve as an immunotherapeutic target for AML with hyperleukocytosis in children.
