The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
21
12
2022
accepted:
31
03
2023
revised:
28
03
2023
medline:
8
6
2023
pubmed:
27
4
2023
entrez:
26
4
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37100882
doi: 10.1038/s41375-023-01895-z
pii: 10.1038/s41375-023-01895-z
pmc: PMC10132433
doi:
Substances chimiques
Early Growth Response Protein 3
144516-98-3
EGR3 protein, human
0
Myeloid-Lymphoid Leukemia Protein
149025-06-9
KMT2A protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1216-1233Informations de copyright
© 2023. The Author(s).
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