Analysis of rare driving events in pediatric acute myeloid leukemia

Sanne Noort, Jolieke van Oosterwijk, Jing Ma, Elizabeth A.R. Garfinkle, Stephanie Nance, Michael Walsh, Guangchun Song, Dirk Reinhardt, Martina Pigazzi, Franco Locatelli, Henrik Hasle, Jonas Abrahamsson, Marie Jarosova, Charikleia Kelaidi, Sophia Polychronopoulou, Marry M. van den Heuvel-Eibrink, Maarten Fornerod, Tanja A. Gruber, C. Michel Zwaan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Downloads (Pure)


Elucidating genetic aberrations in pediatric acute myeloid leukemia (AML) provides insight in biology and may impact on risk-group stratification and clinical outcome. This study aimed to detect such aberrations in a selected series of samples without known (cyto)genetic aberration using molecular profiling. A cohort of 161 patients was selected from various study groups: DCOG, BFM, SJCRH, NOPHO and AEIOP. Samples were analyzed using RNA sequencing (n=152), whole exome (n=135) and/or whole genome sequencing (n=100). In 70 of 156 patients (45%), of whom RNA sequencing or whole genome sequencing was available, rearrangements were detected, 22 of which were novel; five involving ERG rearrangements and four NPM1 rearrangements. ERG rearrangements showed self-renewal capacity in vitro, and a distinct gene expression pattern. Gene set enrichment analysis of this cluster showed upregulation of gene sets derived from Ewing sarcoma, which was confirmed comparing gene expression profiles of AML and Ewing sarcoma. Furthermore, NPM1-rearranged cases showed cytoplasmic NPM1 localization and revealed HOXA/B gene overexpression, as described for NPM1 mutated cases. Single-gene mutations as identified in adult AML were rare. Patients had a median of 24 coding mutations (range, 7-159). Novel recurrent mutations were detected in UBTF (n=10), a regulator of RNA transcription. In 75% of patients an aberration with a prognostic impact could be detected. Therefore, we suggest these techniques need to become standard of care in diagnostics.

Original languageEnglish
Pages (from-to)48-60
Number of pages13
Issue number1
Early online date28 Jul 2022
Publication statusPublished - Jan 2023

Bibliographical note

Publisher Copyright:
©2023 Ferrata Storti Foundation.


Dive into the research topics of 'Analysis of rare driving events in pediatric acute myeloid leukemia'. Together they form a unique fingerprint.

Cite this