TY - JOUR
T1 - Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators
AU - for the Berlin-Frankfurt-Munster Study Group (BFM)
AU - for the Dutch Children’s Oncology Group (DCOG)
AU - for the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP);
AU - for the Nordic Society for Pediatric Hematology and Oncology (NOPHO)
AU - for the Dutch Children’s Oncology Group (DCOG);
AU - for St. Jude Children’s Research Hospital Study Group (SJCRH)
AU - Fornerod, Maarten
AU - Ma, Jing
AU - Noort, Sanne
AU - Liu, Yu
AU - Walsh, Michael P.
AU - Shi, Lei
AU - Nance, Stephanie
AU - Liu, Yanling
AU - Wang, Yuanyuan
AU - Song, Guangchun
AU - Lamprecht, Tamara
AU - Easton, John
AU - Mulder, Heather L.
AU - Yergeau, Donald
AU - Myers, Jacquelyn
AU - Kamens, Jennifer L.
AU - Obeng, Esther A.
AU - Pigazzi, Martina
AU - Jarosova, Marie
AU - Kelaidi, Charikleia
AU - Polychronopoulou, Sophia
AU - Lamba, Jatinder K.
AU - Baker, Sharyn D.
AU - Rubnitz, Jeffrey E.
AU - Reinhardt, Dirk
AU - van den Heuvel-Eibrink, Marry M.
AU - Locatelli, Franco
AU - Hasle, Henrik
AU - Klco, Jeffery M.
AU - Downing, James R.
AU - Zhang, Jinghui
AU - Pounds, Stanley
AU - Zwaan, C. Michel
AU - Gruber, Tanja A.
N1 - Publisher Copyright:
©2021The Authors; Published by the American Association for Cancer Research.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Genomic characterization of pediatric patients with acute myeloid leukemia (AML) has led to the discovery of somatic mutations with prognostic implications. Although gene-expression profiling can differentiate subsets of pediatric AML, its clinical utility in risk stratification remains limited. Here, we evaluate gene expression, pathogenic somatic mutations, and outcome in a cohort of 435 pediatric patients with a spectrum of pediatric myeloid-related acute leukemias for biological subtype discovery. This analysis revealed 63 patients with varying immunophenotypes that span a T-lineage and myeloid continuum designated as acute myeloid/T-lymphoblastic leukemia (AMTL). Within AMTL, two patient subgroups distinguished by FLT3-ITD and PRC2 mutations have different outcomes, demonstrating the impact of mutational composition on survival. Across the cohort, variability in outcomes of patients within isomutational subsets is influenced by transcriptional identity and the presence of a stem cell–like gene-expression signature. Integration of gene expression and somatic mutations leads to improved risk stratification.
AB - Genomic characterization of pediatric patients with acute myeloid leukemia (AML) has led to the discovery of somatic mutations with prognostic implications. Although gene-expression profiling can differentiate subsets of pediatric AML, its clinical utility in risk stratification remains limited. Here, we evaluate gene expression, pathogenic somatic mutations, and outcome in a cohort of 435 pediatric patients with a spectrum of pediatric myeloid-related acute leukemias for biological subtype discovery. This analysis revealed 63 patients with varying immunophenotypes that span a T-lineage and myeloid continuum designated as acute myeloid/T-lymphoblastic leukemia (AMTL). Within AMTL, two patient subgroups distinguished by FLT3-ITD and PRC2 mutations have different outcomes, demonstrating the impact of mutational composition on survival. Across the cohort, variability in outcomes of patients within isomutational subsets is influenced by transcriptional identity and the presence of a stem cell–like gene-expression signature. Integration of gene expression and somatic mutations leads to improved risk stratification.
UR - https://www.scopus.com/pages/publications/85127112874
U2 - 10.1158/2643-3230.BCD-21-0049
DO - 10.1158/2643-3230.BCD-21-0049
M3 - Article
C2 - 34778799
AN - SCOPUS:85127112874
SN - 2643-3230
VL - 2
SP - 586
EP - 599
JO - Blood Cancer Discovery
JF - Blood Cancer Discovery
IS - 6
ER -