TY  - JOUR
AU  - Oksa, Laura
AU  - Moisio, Sanni
AU  - Maqbool, Khurram
AU  - Kramer, Roger
AU  - Nikkilä, Atte
AU  - Jayasingha, Buddika
AU  - Mäkinen, Artturi
AU  - Foroughi-Asl, Hassan
AU  - Rounioja, Samuli
AU  - Suhonen, Janne
AU  - Krali, Olga
AU  - Voutilainen, Miikka
AU  - Lahnalampi, Mari
AU  - Vepsäläinen, Kaisa
AU  - Huang, Sui
AU  - Duque-Afonso, Jesus
AU  - Hauer, Julia
AU  - Nordlund, Jessica
AU  - Wirta, Valtteri
AU  - Lohi, Olli
AU  - Heinäniemi, Merja
TI  - Genomic determinants of therapy response in ETV6::RUNX1 leukemia.
JO  - Leukemia
VL  - 39
IS  - 9
SN  - 0887-6924
CY  - London
PB  - Springer Nature
M1  - DKFZ-2025-01365
SP  - 2125-2139
PY  - 2025
N1  - 2025 Sep;39(9):2125-2139
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40634509
DO  - DOI:10.1038/s41375-025-02683-7
UR  - https://inrepo02.dkfz.de/record/302825
ER  -