ENAGenomicsPATHOLOGY, NYU MEDICAL SCHOOLhttps://www.ebi.ac.uk/ena/browser/view/PRJNA151533Mus musculusT-cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we used a mouse model of T-ALL through the overexpression of the intarcellular transcriptionally active part of Notch1 (N1-IC). This model faithfully recapitulates the major characteristics of the human disease. Comparison of the leukemic cells from peripheral tumors(thymoma) of this mouse model to normal thymic cells Double Positive (DP) for the markers CD4 and CD8 that express very low levels of Notch1 showed major expression changes in pathways controlling the transition from physiology to disease. Further correlation of the data to ChIP-Seq data from the same cell populations led us to identify a hitherto unknown antagonism of the Notch1 oncogenic pathway and the polycomb complex (PRC2) in leukemia. Importantly exome sequencing in primary samples from human patients with T-ALL revealed that the PRC2 complex is frequently mutated and inactivated, further supporting the tumor suppressor role of the complex in this disease. Overall design: Gene expression profiles from CD4+/8+ Double Positive derived from normal thymus and Notch1-IC over-expressing tumors were compared using genome wide mRNA expression profiling by Affymetrix genechip arrays (Mouse 430 2.0).xref:PubMed:22237151ENAMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisxnotch, hN1, Acute T-Cell Leukemias, Lymphocytic Leukemia, Laboratory, Mus domesticus, mouse, 9930111A19Rik, lin-12, House Mouse, Leukemias, mice C57BL/6xCBA/CaJ hybrid, T-Cell Leukemia, Mus muscaris, T-Cell Leukemias, Precursor T Cell Lymphoblastic Lymphoma, Acute., N1, Motch, T-Cell Acute Lymphocytic Leukemia, NOTCH, Acute T-Cell Leukemia, House, Mus, T-Cell, T-Lymphocytic Leukemia, Mus musculus domesticus, acute T cell leukaemia, Precursor T-Cell Lymphoblastic Leukemia, Precursor T Cell Lymphoblastic Leukemia, notch, Mice, Acute T Cell, T-ALL, T-Lymphocytic Leukemias, Lymphoblastic Leukemia, Lymphocytic, xnotch1, Mus musculus, Leukemia, T Cell Leukemia, Acute T-Lymphocytic Leukemias, Swiss, mice, Precursor T-Cell Lymphoblastic Lymphoma, Swiss Mouse, Lymphoblastic, House Mice, Swiss Mice, Acute T-Lymphocytic Leukemia, T Lymphocytic Leukemia, domesticus, Laboratory Mice, Acute, Acute T-Lymphocytic, notch1-a, AOVD1, Precursor T Cell Lymphoblastic Leukemia Lymphoma, Xotch, AOS5, notch-1, Mouse, T Cell, T14, house mouse, TAN1, Tan1, Acute T-Cell, Mis6, Laboratory MousefalseMus musculusNotch1-driven transcriptional changes in a mouse model of T-ALL2025-09-242014-02-11PRJNA151533GSE345541009022237151