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Comparison of the Transcriptomic Signatures in Pediatric and Adult CML
Minyoung Youn1, Stephanie M Smith1, Alex Gia Lee2
1Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Insights
Pediatric chronic myeloid leukemia (CML) shows distinct molecular differences from adult CML, particularly in gene expression and the Rho pathway, impacting disease biology.
Area of Science:
- Hematology
- Molecular Biology
- Genomics
Background:
- Pediatric and adult chronic myeloid leukemia (CML) exhibit clinical differences, suggesting underlying biological variations.
- Understanding these differences is crucial for targeted therapies in pediatric CML.
Purpose of the Study:
- To investigate unique molecular and transcriptomic signatures in pediatric CML.
- To compare gene expression profiles between pediatric and adult CML CD34+ cells.
Main Methods:
- High-throughput RNA sequencing of CD34+ cells from pediatric and adult CML patients and healthy controls.
- Differential gene expression analysis to identify unique molecular characteristics.
- RT-qPCR validation of key differentially expressed genes.
Main Results:
- 567 differentially expressed genes found in pediatric CML CD34+ cells compared to healthy controls.
- 398 differentially expressed genes identified when comparing pediatric and adult CML CD34+ cells, with notable Rho pathway involvement.
- Specific genes (DLC1, VAV2, ARHGAP27, NCF1, CYBB, S100A8) showed distinct expression patterns in pediatric versus adult CML.
Conclusions:
- Pediatric CML possesses unique molecular characteristics, including Rho pathway dysregulation.
- These molecular differences may explain the distinct clinical presentations of pediatric CML.
- Further research into these unique pathways could lead to novel therapeutic strategies for children with CML.
Abstract:
Children with chronic myeloid leukemia (CML) tend to present with higher white blood counts and larger spleens than adults with CML, suggesting that the biology of pediatric and adult CML may differ. To investigate whether pediatric and adult CML have unique molecular characteristics, we studied the transcriptomic signature of pediatric and adult CML CD34+ cells and healthy pediatric and adult CD34+ control cells. Using high-throughput RNA sequencing, we found 567 genes (207 up- and 360 downregulated) differentially expressed in pediatric CML CD34+ cells compared to pediatric healthy CD34+ cells. Directly comparing pediatric and adult CML CD34+ cells, 398 genes (258 up- and 140 downregulated), including many in the Rho pathway, were differentially expressed in pediatric CML CD34+ cells. Using RT-qPCR to verify differentially expressed genes, VAV2 and ARHGAP27 were significantly upregulated in adult CML CD34+ cells compared to pediatric CML CD34+ cells. NCF1, CYBB, and S100A8 were upregulated in adult CML CD34+ cells but not in pediatric CML CD34+ cells, compared to healthy controls. In contrast, DLC1 was significantly upregulated in pediatric CML CD34+ cells but not in adult CML CD34+ cells, compared to healthy controls. These results demonstrate unique molecular characteristics of pediatric CML, such as dysregulation of the Rho pathway, which may contribute to clinical differences between pediatric and adult patients.
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