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Significance Engineered mouse models of acute leukemia are critical to understanding the biological mechanisms by which a primary oncogene induces disease. While PAX5 fusion proteins are considered primary oncogenic events in B-ALL, their role in leukemia development is ill-known due to the lack of animal models. This report provides a novel and accurate in vivo model for B-ALL induced by PAX5-ELN fusion protein that establishes a preleukemic phase and recapitulates the key features of human disease, including acquired mutations in genes of the JAK/STAT and RAS/MAPK pathways. This study is of general interest, as it allows a better understanding of the biological mechanism by which an oncoprotein perturbs normal B-cell development and leads to pathological B-ALL.

PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice