ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis,Leukemia

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ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis
Leukemia ( IF 12.8 ) Pub Date : 2021-09-17 , DOI: 10.1038/s41375-021-01409-9
Hélène Jakobczyk ₁ , Yan Jiang _{2,

3} , Lydie Debaize ₁ , Benoit Soubise ₂ , Stéphane Avner ₁ , Aurélien A Sérandour ₄ , Jérémie Rouger-Gaudichon ₅ , Anne-Gaëlle Rio ₁ , Jason S Carroll ₆ , Hana Raslova _{7,

8} , David Gilot ₉ , Ziling Liu ₁₀ , Jocelyne Demengeot ₁₁ , Gilles Salbert ₁ , Nathalie Douet-Guilbert _{2,

12} , Laurent Corcos ₂ , Marie-Dominique Galibert _{1,

13} , Virginie Gandemer _{1,

14} , Marie-Bérengère Troadec _{1,

2,

12}

Affiliation

Univ Rennes 1, CNRS, IGDR (Institut de génétique et développement de Rennes) - UMR 6290, Rennes, France.
Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.
Department of Hematology, The First Hospital of Jilin University, Changchun, China.
Université de Nantes, Ecole Centrale de Nantes, Inserm, CRCINA, Nantes, France.
Department of Pediatric Oncology and Hematology, University Hospital, Caen, France.
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif, France.
Equipe labellisée Ligue Nationale contre le Cancer, Villejuif, France.
INSERM, Université Rennes, CLCC Eugène Marquis, UMR_S 1242, Rennes, France.
Cancer Center, The First Hospital of Jilin University, Changchun, China.
Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, Oeiras, Portugal.
CHRU Brest, Service de génétique, laboratoire de génétique chromosomique, Brest, France.
Centre Hospitalier Universitaire de Rennes (CHU-Rennes), Service de Génétique et Génomique Moléculaire, Rennes, France.
Centre Hospitalier Universitaire de Rennes (CHU-Rennes), Department of pediatric hemato-oncology, Rennes, France.

ETV6-RUNX1 and RUNX1 directly promote RAG1 expression.
ETV6-RUNX1 and RUNX1 preferentially bind to the −1200 bp enhancer of RAG1 and the −80 bp promoter of RAG1 gene respectively, and compete for these bindings.
ETV6-RUNX1 and RUNX1 induce an excessive RAG recombinase activity.
ETV6-RUNX1 participates directly in two events of the multi-hit ALL leukemogenesis: as an initiating event and as an activator of RAG1 expression.