biostudies-literatureMercher TNIDDK NIH HHSNCI NIH HHS852-64https://www.ebi.ac.uk/biostudies/studies/S-EPMC2662544biostudies-literatureUnknown119(4)Acute megakaryoblastic leukemia (AMKL) is a form of acute myeloid leukemia (AML) associated with a poor prognosis. The genetics and pathophysiology of AMKL are not well understood. We generated a knockin mouse model of the one twenty-two-megakaryocytic acute leukemia (OTT-MAL) fusion oncogene that results from the t(1;22)(p13;q13) translocation specifically associated with a subtype of pediatric AMKL. We report here that OTT-MAL expression deregulated transcriptional activity of the canonical Notch signaling pathway transcription factor recombination signal binding protein for immunoglobulin kappa J region (RBPJ) and caused abnormal fetal megakaryopoiesis. Furthermore, cooperation between OTT-MAL and an activating mutation of the thrombopoietin receptor myeloproliferative leukemia virus onThe Journal of clinical investigationThe OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model.PMC2662544P01 CA066996CA66996DK50654K08 CA111399P01 DK050654U01 CA105423Cornejo MGCagnard NBernard OAMoore SAWilliams IRJesneck JLLevine RLMercher TCullen DRaffel GDBaudry-Bluteau DBourquin JPVainchenker WPikman YLee BHAkashi KGilliland DGGiovannini MShigematsu HfalseThe OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model.Acute megakaryoblastic leukemia (AMKL) is a form of acute myeloid leukemia (AML) associated with a poor prognosis. The genetics and pathophysiology of AMKL are not well understood. We generated a knockin mouse model of the one twenty-two-megakaryocytic acute leukemia (OTT-MAL) fusion oncogene that results from the t(1;22)(p13;q13) translocation specifically associated with a subtype of pediatric AMKL. We report here that OTT-MAL expression deregulated transcriptional activity of the canonical Notch signaling pathway transcription factor recombination signal binding protein for immunoglobulin kappa J region (RBPJ) and caused abnormal fetal megakaryopoiesis. Furthermore, cooperation between OTT-MAL and an activating mutation of the thrombopoietin receptor myeloproliferative leukemia virus on2009-01-01T00:00:00Z2009 Apr2026-05-03T20:49:08.192Z2019-03-27T00:21:29ZS-EPMC26625441928709510.1172/JCI3590110.1172/jci35901