The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome.

Leukemia 2023 Jun

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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. © 2023. The Author(s).

Citation

Marius Külp, Patrizia Larghero, Julia Alten, Gunnar Cario, Cornelia Eckert, Aurélie Caye-Eude, Hélène Cavé, Tessa Schmachtel, Michela Bardini, Giovanni Cazzaniga, Paola De Lorenzo, Maria Grazia Valsecchi, Halvard Bonig, Claus Meyer, Michael A Rieger, Rolf Marschalek. The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome. Leukemia. 2023 Jun;37(6):1216-1233