npj Precision Oncology (Dec 2023)
Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia
- Olga Krali,
- Yanara Marincevic-Zuniga,
- Gustav Arvidsson,
- Anna Pia Enblad,
- Anders Lundmark,
- Shumaila Sayyab,
- Vasilios Zachariadis,
- Merja Heinäniemi,
- Janne Suhonen,
- Laura Oksa,
- Kaisa Vepsäläinen,
- Ingegerd Öfverholm,
- Gisela Barbany,
- Ann Nordgren,
- Henrik Lilljebjörn,
- Thoas Fioretos,
- Hans O. Madsen,
- Hanne Vibeke Marquart,
- Trond Flaegstad,
- Erik Forestier,
- Ólafur G. Jónsson,
- Jukka Kanerva,
- Olli Lohi,
- Ulrika Norén-Nyström,
- Kjeld Schmiegelow,
- Arja Harila,
- Mats Heyman,
- Gudmar Lönnerholm,
- Ann-Christine Syvänen,
- Jessica Nordlund
Affiliations
- Olga Krali
- Department of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University
- Yanara Marincevic-Zuniga
- Department of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University
- Gustav Arvidsson
- Department of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University
- Anna Pia Enblad
- Department of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University
- Anders Lundmark
- Department of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University
- Shumaila Sayyab
- Department of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University
- Vasilios Zachariadis
- Department of Oncology-Pathology, Karolinska Institutet
- Merja Heinäniemi
- Institute of Biomedicine, School of Medicine, University of Eastern Finland
- Janne Suhonen
- Institute of Biomedicine, School of Medicine, University of Eastern Finland
- Laura Oksa
- Tampere Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
- Kaisa Vepsäläinen
- Department of Pediatrics, Kuopio University Hospital
- Ingegerd Öfverholm
- Department of Oncology-Pathology, Karolinska Institutet
- Gisela Barbany
- Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet
- Ann Nordgren
- Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet
- Henrik Lilljebjörn
- Division of Clinical Genetics, Dept. of Laboratory Medicine, Lund University
- Thoas Fioretos
- Division of Clinical Genetics, Dept. of Laboratory Medicine, Lund University
- Hans O. Madsen
- Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet
- Hanne Vibeke Marquart
- Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet
- Trond Flaegstad
- Department of Pediatrics, Tromsø University and University Hospital
- Erik Forestier
- For the Nordic Society of Pediatric Hematology and Oncology (NOPHO)
- Ólafur G. Jónsson
- For the Nordic Society of Pediatric Hematology and Oncology (NOPHO)
- Jukka Kanerva
- For the Nordic Society of Pediatric Hematology and Oncology (NOPHO)
- Olli Lohi
- Tampere Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
- Ulrika Norén-Nyström
- For the Nordic Society of Pediatric Hematology and Oncology (NOPHO)
- Kjeld Schmiegelow
- For the Nordic Society of Pediatric Hematology and Oncology (NOPHO)
- Arja Harila
- Department of Women’s and Children’s Health, Uppsala University
- Mats Heyman
- For the Nordic Society of Pediatric Hematology and Oncology (NOPHO)
- Gudmar Lönnerholm
- Department of Women’s and Children’s Health, Uppsala University
- Ann-Christine Syvänen
- Department of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University
- Jessica Nordlund
- Department of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University
- DOI
- https://doi.org/10.1038/s41698-023-00479-5
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 13
Abstract
Abstract Genomic analyses have redefined the molecular subgrouping of pediatric acute lymphoblastic leukemia (ALL). Molecular subgroups guide risk-stratification and targeted therapies, but outcomes of recently identified subtypes are often unclear, owing to limited cases with comprehensive profiling and cross-protocol studies. We developed a machine learning tool (ALLIUM) for the molecular subclassification of ALL in retrospective cohorts as well as for up-front diagnostics. ALLIUM uses DNA methylation and gene expression data from 1131 Nordic ALL patients to predict 17 ALL subtypes with high accuracy. ALLIUM was used to revise and verify the molecular subtype of 281 B-cell precursor ALL (BCP-ALL) cases with previously undefined molecular phenotype, resulting in a single revised subtype for 81.5% of these cases. Our study shows the power of combining DNA methylation and gene expression data for resolving ALL subtypes and provides a comprehensive population-based retrospective cohort study of molecular subtype frequencies in the Nordic countries.
