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@ARTICLE{Oksa:302825,
author = {L. Oksa and S. Moisio and K. Maqbool and R. Kramer and A.
Nikkilä and B. Jayasingha and A. Mäkinen and H.
Foroughi-Asl and S. Rounioja and J. Suhonen and O. Krali and
M. Voutilainen and M. Lahnalampi and K. Vepsäläinen and S.
Huang and J. Duque-Afonso and J. Hauer$^*$ and J. Nordlund
and V. Wirta and O. Lohi and M. Heinäniemi},
title = {{G}enomic determinants of therapy response in
{ETV}6::{RUNX}1 leukemia.},
journal = {Leukemia},
volume = {39},
number = {9},
issn = {0887-6924},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01365},
pages = {2125-2139},
year = {2025},
note = {2025 Sep;39(9):2125-2139},
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.},
cin = {MU01},
ddc = {610},
cid = {I:(DE-He78)MU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40634509},
doi = {10.1038/s41375-025-02683-7},
url = {https://inrepo02.dkfz.de/record/302825},
}