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Published on: March 26, 2018
Exploring the Role of Macrophage Marker CD68 in Pediatric Acute Myeloid Leukemia
Laurens Van Camp1,2,3, Jolien Vanhooren1,2,3, Barbara Depreter4,5
1Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, 9000 Ghent, Belgium.
Abstract:
Pediatric acute myeloid leukemia (pedAML) is a childhood malignancy with relapse rates of approximately 30%. CD68, a macrophage marker involved in phagocytosis and macrophage recruitment, may contribute to AML biology. We analyzed CD68 expression using the TARGET database and performed survival analyses, mRNA/protein profiling, and functional assays in AML cell lines, pedAML samples, and cord blood samples. High CD68 transcript levels correlated with KMT2A-rearrangements and inversion 16. Survival analysis showed that high CD68 predicted worse event-free survival, though not independently in a multivariate analysis. Flow cytometry confirmed higher CD68 expression in 7/8 pedAML samples compared to cord blood samples. Functionally, CD68 knockdown reduced proliferation and increased drug sensitivity, while overexpression promoted growth and resistance. Gene set enrichment analysis (GSEA) indicated enrichment of MAPK signaling, AP-1-mediated stress response, and epithelial-mesenchymal transition (EMT)/migration-associated pathways in CD68-high models. Together, these findings suggest that CD68 contributes to a pro-tumorigenic and stress-adaptive phenotype in pedAML and may represent a biologically relevant therapeutic target.
Insights
High CD68 expression in pediatric acute myeloid leukemia (pedAML) correlates with poor outcomes and promotes tumor growth. Reducing CD68 may improve treatment sensitivity in childhood leukemia.
Area of Science:
- Hematology
- Cancer Biology
- Molecular Oncology
Background:
- Pediatric acute myeloid leukemia (pedAML) has a significant relapse rate.
- CD68, a macrophage marker, is implicated in myeloid leukemia biology.
Purpose of the Study:
- To investigate the role and prognostic significance of CD68 in pedAML.
- To explore the functional impact of CD68 on leukemia cell behavior.
Main Methods:
- Analysis of CD68 expression in the TARGET database.
- Survival analyses, mRNA/protein profiling, and functional assays in cell lines and patient samples.
- Gene set enrichment analysis (GSEA) was performed.
Main Results:
- High CD68 transcript levels were associated with specific genetic alterations (KMT2A-rearrangements, inversion 16).
- Elevated CD68 predicted worse event-free survival in univariate analysis.
- CD68 knockdown decreased proliferation and increased drug sensitivity; overexpression promoted growth and resistance.
Conclusions:
- CD68 expression is linked to a pro-tumorigenic and stress-adaptive phenotype in pedAML.
- CD68 may serve as a potential therapeutic target for childhood AML.
