ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis
Hélène Jakobczyk, Yan Jiang, Lydie Debaize, Benoît Soubise, Stéphane Avner, Aurélien A. Sérandour, Jérémie Rouger, Anne-Gaëlle Rio, Jason S. Carroll, Hana Raslová, David Gilot, Ziling Liu, Jocelyne Demengeot, Gilles Salbert, Nathalie Douet‐Guilbert, Laurent Corcos, Marie‐Dominique Galibert, Virginie Gandemer, Marie‐Bérengère Troadec
Abstract
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.