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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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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
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author 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
author_facet 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
author_sort Külp, Marius
collection PubMed
description 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]
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spelling pubmed-101324332023-04-27 The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome 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 Leukemia Article 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] Nature Publishing Group UK 2023-04-26 2023 /pmc/articles/PMC10132433/ /pubmed/37100882 http://dx.doi.org/10.1038/s41375-023-01895-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome
title The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome
title_full The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome
title_fullStr The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome
title_full_unstemmed The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome
title_short The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome
title_sort egr3 regulome of infant kmt2a-r acute lymphoblastic leukemia identifies differential expression of b-lineage genes predictive for outcome
topic Article
url 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
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