Related Experiment Video
Updated: Jun 14, 2026
Mapping Infant Immunity with Minimal Input: Integrative Single-Cell and Multiomic Profiling
Published on: April 3, 2026
Gene expression profiles of infant acute lymphoblastic leukaemia and its prognostically distinct subsets
1Molecular Oncology and Drug Discovery Program, Parker Hughes Institute, St. Paul, MN, USA.
Insights
Infant acute lymphoblastic leukemia (ALL) shows distinct gene expression, with overexpressed survival genes. Targeting the JAK-STAT pathway with JAK3 inhibitors offers a promising therapeutic strategy for infant ALL.
Area of Science:
- Oncology
- Molecular Biology
- Pediatric Hematology
Background:
- Acute lymphoblastic leukemia (ALL) in infants presents unique biological and clinical challenges compared to pediatric ALL.
- Understanding the distinct molecular drivers of infant ALL is crucial for developing targeted therapies.
Purpose of the Study:
- To compare gene expression profiles between infant and pediatric ALL.
- To identify key molecular pathways and potential therapeutic targets in infant ALL.
Main Methods:
- Comparative analysis of gene expression profiles from infant and pediatric ALL patient samples.
- Investigation of the JAK-STAT signaling pathway in infant ALL cells.
- Assessment of apoptosis induction by JAK inhibitors in infant ALL cells.
Main Results:
- Infant ALL exhibits a distinct pathognomonic transcriptome characterized by overexpression of mitogenic and anti-apoptotic genes.
- Infant ALL cells show elevated expression of cytokines activating the JAK-STAT pathway (e.g., IL-1a, IL-1b, IL-2, IL-7).
- The JAK/STAT pathway is constitutively active in CD10(-) infant ALL cells, and JAK3 or pan-JAK inhibitors induce apoptosis.
Conclusions:
- Significant biological differences exist between infant and pediatric high-risk ALL.
- The JAK-STAT signaling pathway, particularly JAK3, is a critical therapeutic target for infant ALL.
- Targeting JAK3 may disrupt deregulated anti-apoptotic STAT3 and STAT5 signaling in infant ALL.
Abstract:
This study compared the gene expression profiles of primary leukaemic cells from infants versus children with acute lymphoblastic leukaemia (ALL). Our analyses provided unprecedented evidence that remarkably different pathognomonic transcriptomes dominate the biology of infant versus paediatric high risk ALL. The genetic signature of infant ALL is characterized by concomitant overexpression of mitogenic and anti-apoptotic genes, some of which have been associated with early relapse in ALL. Our study demonstrated that primary leukaemia cells from infant ALL patients expressed significantly higher levels of genes for cytokines that mediate their biological effects through stimulation of the JAK-STAT signal transduction pathway including interleukin 1a, interleukin 1b, interleukin 2, and interleukin 7. We further showed that the JAK/STAT signalling pathway is constitutively active in CD10(-) infant ALL cells and treatment with a JAK3 inhibitor or a pan-JAK kinase inhibitor effectively triggered their apoptosis. These findings identified JAK3 as an attractive molecular target for disrupting the constitutively deregulated anti-apoptotic STAT3 and STAT5 signalling pathways in infant ALL cells.
