The circulating blood proteome of childhood acute leukemia
Anna Pia Enblad 1,2,3*, Maria A. Globisch 1,2*, Dea Gogishvili 1,2, Tiina Tuononen 4, Olga Krali 1,2, Anders Lundmark 1,2, Laura Oksa 5,6, Charlotte Hjort 7,8, Mariya Lysenkova Wiklander 1,2, Linda Holmfeldt 9, Mikael Åberg 1,2, Josefine Palle 3, Signe Modvig 7,8, Olli Lohi 5,6, Merja Heinäniemi 4, Arja Harila 3+ & Jessica Nordlund 1,2+.
Affiliations:
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
- SciLifeLab, Uppsala University, Uppsala, Sweden
- Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
- The Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
- Tampere Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Tampere University Hospital, Tays Cancer Centre, Tampere, Finland
- Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
*These authors contributed equally to this work
+Correspondence can be addressed to jessica.nordlund@medsci.uu.se or arja.harila@uu.se
The circulating blood proteome provides a systemic readout of disease biology and holds promise for advancing diagnostics and disease monitoring in pediatric leukemia. Here, we profiled 3072 proteins in diagnostic serum from 54 children with acute lymphoblastic leukemia (ALL), 21 with acute myeloid leukemia (AML), and 12 healthy controls using the Olink Proximity Extension Assay. We observed profound alterations in circulating protein levels in leukemia patients compared with controls and identified immunophenotype-specific proteins, including SIGLEC15 in B-cell precursor ALL (BCP-ALL), NOTCH1 in T-ALL, and CEBPA in AML, all which remained high even in patients with low (<20%) or no peripheral blood blasts. Within BCP-ALL, molecular subtypes were reflected in the circulating proteome; for example, DSC2 and PTPRK were elevated in ETV6::RUNX1-positive cases, while IL-6R and ADAM8 were higher in High Hyperdiploid cases. Angiogenic growth factors decreased across all leukemia patients compared with controls, suggesting a fragile peripheral vasculature at diagnosis. Integration with external datasets revealed the likely cellular source of abundant proteins and examination of an external cohort validated our subtype-specific findings. Together, these results define shared and distinct proteomic signatures across pediatric acute leukemias and highlight candidate biomarkers for diagnostics and disease monitoring.
Figure 1. The study overview.
The /scripts directory contains the code used for data analysis and figure generation. The /data directory contains supplementary results, including limma output, protein features for the full human proteome and biomarker subset (secondary structure, PTM annotations, subcellular localization, extracellular vesicle association predictions, and other relevant global (protein-level) annotations & predictions).
Note: Code is provided for transparency and reproducibility purposes. As the original Olink data cannot be shared publicly, most scripts cannot be executed as-is.