Deciphering molecular heterogeneity in pediatric AML using a cancer vs. normal transcriptomic approach
Barbara Depreter1, Barbara De Moerloose2,3,4, Karl Vandepoele3,5
1Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium. barbara.depreter@uzbrussel.be.
Pediatric Research
|October 17, 2020
Summary
Relapsed pediatric acute myeloid leukemia (pedAML) has new therapeutic targets. Researchers identified novel overexpressed and downregulated genes in leukemic stem cells and blasts, offering potential biomarkers and treatment strategies for pedAML.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Pediatric acute myeloid leukemia (pedAML) has a high relapse rate, necessitating better understanding of its molecular underpinnings.
- Leukemic subpopulations, such as leukemic stem cells (LSC) and leukemic blasts (L-blast), play crucial roles in disease progression and relapse.
- Identifying transcriptomic differences in these subpopulations can reveal novel biomarkers and therapeutic targets.
Purpose of the Study:
- To delineate the transcriptomic profile of leukemic stem cells (LSC) and leukemic blasts (L-blast) in pediatric acute myeloid leukemia (pedAML).
- To compare the gene expression patterns of LSC and L-blast from pedAML patients with their normal counterparts, hematopoietic stem cells (HSC) and control myeloblasts (C-blast).
- To identify novel differentially expressed genes and perturbed biological networks for potential therapeutic intervention in pedAML.
Main Methods:
- Microarray profiling and quantitative PCR were used to measure transcript expression.
- Samples included LSC (n=24) and L-blast (n=25) from pedAML patients, and HSC (n=19) and C-blast (n=20) from healthy controls.
- Gene set enrichment analysis and STRING analysis were employed to identify significant gene sets and protein associations.
Main Results:
- Numerous significantly overexpressed genes were identified in LSC and L-blast, with CDKN1A, CFP, CFD (LSC) and HOMER3, CTSA, GADD45B (L-blast) being of particular interest.
- Eleven downregulated targets in LSC, including MYCT1, PBX1, and PTPRD, were identified as potential tumor suppressor genes.
- Perturbed biological networks included inflammatory and immune dysregulation in LSC, and dysregulated metabolic profiles in L-blast.
Conclusions:
- The study highlights the importance of considering cell population heterogeneity in pedAML.
- Novel transcriptional targets were discovered, offering potential for functional evaluation and targeted therapy in pedAML.
- The findings provide a deeper understanding of pedAML molecular pathogenesis and identify potential biomarkers for risk stratification and treatment.
