Journal Article

DKFZ-2025-01365

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genomic determinants of therapy response in ETV6::RUNX1 leukemia.

Oksa, L. ; Moisio, S. ; Maqbool, K. ; Kramer, R. ; Nikkilä, A. ; Jayasingha, B. ; Mäkinen, A. ; Foroughi-Asl, H. ; Rounioja, S. ; Suhonen, J. ; Krali, O. ; Voutilainen, M. ; Lahnalampi, M. ; Vepsäläinen, K. ; Huang, S. ; Duque-Afonso, J. ; Hauer, J.DKFZ* ; Nordlund, J. ; Wirta, V. ; Lohi, O. ; Heinäniemi, M.

2025
Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41375-025-02683-7

Abstract: ETV6::RUNX1 leukemia is the second most common subtype of childhood B cell acute lymphoblastic leukemia (B-ALL). Although it generally has a low relapse risk, a significant proportion of B-ALL relapses occur within this subtype due to its relatively high incidence. Measurable residual disease at the end of induction therapy is a well-established biomarker predicting treatment outcomes, while no genomic biomarkers are routinely applied in clinics. In this study, we used multiomic data from ETV6::RUNX1 leukemias to identify genomic features predictive of therapy response at disease presentation. In the deeply characterized sub-cohort we discovered that fast-responding cases frequently exhibited the APOBEC mutational signature and the gene expression signature of high cell cycle activity. In contrast, rearrangements of IGK genes were more frequent in slow responders. Additionally, response-related mutations were identified in transcriptional regulators and tumor suppressor genes (INTS1, NF1, TP53). Copy number analysis revealed that fast responders harbored more frequent deletions of chr12 p-arm, leading to transcriptomic changes affecting genes associated with induction therapy response (KRAS, FKBP4), while a shorter gain in chr12 was more common in slow responders. The identified genetic and transcriptomic markers of treatment sensitivity pave the way for improved disease classification at presentation, potentially improving clinical outcomes.

Note: 2025 Sep;39(9):2125-2139

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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