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

doi:10.1038/s41698-023-00479-5

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 ForestierÓlafur G Jónsson, Jukka Kanerva, Olli Lohi, Ulrika Norén-Nyström, Kjeld Schmiegelow, Arja Harila, Mats Heyman, Gudmar Lönnerholm, Ann-Christine Syvänen, Jessica Nordlund^*

^*Corresponding author af dette arbejde

14 Citationer (Scopus)

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.

Originalsprog	Engelsk
Artikelnummer	131
Tidsskrift	NPJ precision oncology
Vol/bind	7
Udgave nummer	1
ISSN	2397-768X
DOI	https://doi.org/10.1038/s41698-023-00479-5
Status	Udgivet - 8 dec. 2023

Adgang til dokumentet

10.1038/s41698-023-00479-5

Andre filer og links

Link to publication in Scopus

Citationsformater

Krali, O., Marincevic-Zuniga, Y., Arvidsson, G., Enblad, A. P., Lundmark, A., Sayyab, S., Zachariadis, V., Heinäniemi, M., Suhonen, J., Oksa, L., Vepsäläinen, K., Öfverholm, I., Barbany, G., Nordgren, A., Lilljebjörn, H., Fioretos, T., Madsen, H. O., Marquart, H. V., Flaegstad, T., ... Nordlund, J. (2023). Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia. NPJ precision oncology, 7(1), Artikel 131. https://doi.org/10.1038/s41698-023-00479-5

Krali, O, Marincevic-Zuniga, Y, Arvidsson, G, Enblad, AP, Lundmark, A, Sayyab, S, Zachariadis, V, Heinäniemi, M, Suhonen, J, Oksa, L, Vepsäläinen, K, Öfverholm, I, Barbany, G, Nordgren, A, Lilljebjörn, H, Fioretos, T, Madsen, HO , Marquart, HV, Flaegstad, T, Forestier, E, Jónsson, ÓG, Kanerva, J, Lohi, O, Norén-Nyström, U, Schmiegelow, K, Harila, A, Heyman, M, Lönnerholm, G, Syvänen, A-C & Nordlund, J 2023, 'Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia', NPJ precision oncology, bind 7, nr. 1, 131. https://doi.org/10.1038/s41698-023-00479-5

@article{79966e9300e14758a347a0b691f595f5,

title = "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 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.",

author = "Olga Krali and Yanara Marincevic-Zuniga and Gustav Arvidsson and Enblad, {Anna Pia} and Anders Lundmark and Shumaila Sayyab and Vasilios Zachariadis and Merja Hein{\"a}niemi and Janne Suhonen and Laura Oksa and Kaisa Veps{\"a}l{\"a}inen and Ingegerd {\"O}fverholm and Gisela Barbany and Ann Nordgren and Henrik Lilljebj{\"o}rn and Thoas Fioretos and Madsen, {Hans O} and Marquart, {Hanne Vibeke} and Trond Flaegstad and Erik Forestier and J{\'o}nsson, {{\'O}lafur G} and Jukka Kanerva and Olli Lohi and Ulrika Nor{\'e}n-Nystr{\"o}m and Kjeld Schmiegelow and Arja Harila and Mats Heyman and Gudmar L{\"o}nnerholm and Ann-Christine Syv{\"a}nen and Jessica Nordlund",

note = "{\textcopyright} 2023. The Author(s).",

year = "2023",

month = dec,

day = "8",

doi = "10.1038/s41698-023-00479-5",

language = "English",

volume = "7",

journal = "NPJ precision oncology",

issn = "2397-768X",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia

AU - Krali, Olga

AU - Marincevic-Zuniga, Yanara

AU - Arvidsson, Gustav

AU - Enblad, Anna Pia

AU - Lundmark, Anders

AU - Sayyab, Shumaila

AU - Zachariadis, Vasilios

AU - Heinäniemi, Merja

AU - Suhonen, Janne

AU - Oksa, Laura

AU - Vepsäläinen, Kaisa

AU - Öfverholm, Ingegerd

AU - Barbany, Gisela

AU - Nordgren, Ann

AU - Lilljebjörn, Henrik

AU - Fioretos, Thoas

AU - Madsen, Hans O

AU - Marquart, Hanne Vibeke

AU - Flaegstad, Trond

AU - Forestier, Erik

AU - Jónsson, Ólafur G

AU - Kanerva, Jukka

AU - Lohi, Olli

AU - Norén-Nyström, Ulrika

AU - Schmiegelow, Kjeld

AU - Harila, Arja

AU - Heyman, Mats

AU - Lönnerholm, Gudmar

AU - Syvänen, Ann-Christine

AU - Nordlund, Jessica

PY - 2023/12/8

Y1 - 2023/12/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85179355296&partnerID=8YFLogxK

U2 - 10.1038/s41698-023-00479-5

DO - 10.1038/s41698-023-00479-5

M3 - Journal article

C2 - 38066241

SN - 2397-768X

VL - 7

JO - NPJ precision oncology

JF - NPJ precision oncology

IS - 1

M1 - 131

ER -

Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia

Abstract

Adgang til dokumentet

Andre filer og links

Fingeraftryk

Citationsformater