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

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 ass...

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Detalles Bibliográficos
Autores principales: Külp, Marius, Larghero, Patrizia, Alten, Julia, Cario, Gunnar, Eckert, Cornelia, Caye-Eude, Aurélie, Cavé, Hélène, Schmachtel, Tessa, Bardini, Michela, Cazzaniga, Giovanni, De Lorenzo, Paola, Valsecchi, Maria Grazia, Bonig, Halvard, Meyer, Claus, Rieger, Michael A., Marschalek, Rolf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132433/
https://www.ncbi.nlm.nih.gov/pubmed/37100882
http://dx.doi.org/10.1038/s41375-023-01895-z
Descripción
Sumario: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. [Image: see text]