TY  - JOUR
AU  - Külp, Marius
AU  - Larghero, Patrizia
AU  - Alten, Julia
AU  - Cario, Gunnar
AU  - Eckert, Cornelia
AU  - Caye-Eude, Aurélie
AU  - Cavé, Hélène
AU  - Schmachtel, Tessa
AU  - Bardini, Michela
AU  - Cazzaniga, Giovanni
AU  - De Lorenzo, Paola
AU  - Valsecchi, Maria Grazia
AU  - Bonig, Halvard
AU  - Meyer, Claus
AU  - Rieger, Michael A
AU  - Marschalek, Rolf
TI  - The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome.
JO  - Leukemia
VL  - 37
IS  - 6
SN  - 0887-6924
CY  - London
PB  - Springer Nature
M1  - DKFZ-2023-00824
SP  - 1216-1233
PY  - 2023
N1  - 2023 Jun;37(6):1216-1233
AB  - KMT2A-rearranged acute lymphoblastic infant leukemia (KMT2A-r iALL) is associated with outsize risk of relapse and relapse mortality. We previously reported strong upregulation of the immediate early gene EGR3 in KMT2A::AFF1 iALL at relapse; now we provide analyses of the EGR3 regulome, which we assessed through binding and expression target analysis of an EGR3-overexpressing t(4;11) cell culture model. Our data identify EGR3 as a regulator of early B-lineage commitment. Principal component analysis of 50 KMT2A-r iALL patients at diagnosis and 18 at relapse provided strictly dichotomous separation of patients based on the expression of four B-lineage genes. Absence of B-lineage gene expression translates to more than two-fold poorer long-term event-free survival. In conclusion, our study presents four B-lineage genes with prognostic significance, suitable for gene expression-based risk stratification of KMT2A-r iALL patients.
LB  - PUB:(DE-HGF)16
C6  - pmid:37100882
DO  - DOI:10.1038/s41375-023-01895-z
UR  - https://inrepo02.dkfz.de/record/275622
ER  -