Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia
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 profilin...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-023-00479-5 |
| _version_ | 1827590774922936320 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Olga Krali |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:21:31Z |
| format | Article |
| id | doaj.art-7542b6ffc9a04cf2bdda7eb58e446d0d |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-09T01:21:31Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-7542b6ffc9a04cf2bdda7eb58e446d0d2023-12-10T12:05:50ZengNature Portfolionpj Precision Oncology2397-768X2023-12-017111310.1038/s41698-023-00479-5Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemiaOlga Krali0Yanara Marincevic-Zuniga1Gustav Arvidsson2Anna Pia Enblad3Anders Lundmark4Shumaila Sayyab5Vasilios Zachariadis6Merja Heinäniemi7Janne Suhonen8Laura Oksa9Kaisa Vepsäläinen10Ingegerd Öfverholm11Gisela Barbany12Ann Nordgren13Henrik Lilljebjörn14Thoas Fioretos15Hans O. Madsen16Hanne Vibeke Marquart17Trond Flaegstad18Erik Forestier19Ólafur G. Jónsson20Jukka Kanerva21Olli Lohi22Ulrika Norén-Nyström23Kjeld Schmiegelow24Arja Harila25Mats Heyman26Gudmar Lönnerholm27Ann-Christine Syvänen28Jessica Nordlund29Department of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala UniversityDepartment of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala UniversityDepartment of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala UniversityDepartment of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala UniversityDepartment of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala UniversityDepartment of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala UniversityDepartment of Oncology-Pathology, Karolinska InstitutetInstitute of Biomedicine, School of Medicine, University of Eastern FinlandInstitute of Biomedicine, School of Medicine, University of Eastern FinlandTampere Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere UniversityDepartment of Pediatrics, Kuopio University HospitalDepartment of Oncology-Pathology, Karolinska InstitutetDepartment of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska InstitutetDepartment of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska InstitutetDivision of Clinical Genetics, Dept. of Laboratory Medicine, Lund UniversityDivision of Clinical Genetics, Dept. of Laboratory Medicine, Lund UniversityDepartment of Clinical Immunology, Copenhagen University Hospital RigshospitaletDepartment of Clinical Immunology, Copenhagen University Hospital RigshospitaletDepartment of Pediatrics, Tromsø University and University HospitalFor the Nordic Society of Pediatric Hematology and Oncology (NOPHO)For the Nordic Society of Pediatric Hematology and Oncology (NOPHO)For the Nordic Society of Pediatric Hematology and Oncology (NOPHO)Tampere Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere UniversityFor the Nordic Society of Pediatric Hematology and Oncology (NOPHO)For the Nordic Society of Pediatric Hematology and Oncology (NOPHO)Department of Women’s and Children’s Health, Uppsala UniversityFor the Nordic Society of Pediatric Hematology and Oncology (NOPHO)Department of Women’s and Children’s Health, Uppsala UniversityDepartment of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala UniversityDepartment of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala UniversityAbstract 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.https://doi.org/10.1038/s41698-023-00479-5 |
| spellingShingle | 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 Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia npj Precision Oncology |
| title | Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia |
| title_full | Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia |
| title_fullStr | Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia |
| title_full_unstemmed | Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia |
| title_short | Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia |
| title_sort | multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia |
| url | https://doi.org/10.1038/s41698-023-00479-5 |
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