biostudies-literatureCarr TNIAID NIH HHSNCI NIH HHSNational Institutes of Health845488https://www.ebi.ac.uk/biostudies/studies/S-EPMC8971981biostudies-literatureUnknown13T lymphocyte acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease affecting T cells at multiple stages of their development and is characterized by frequent genomic alterations. The transcription factor LEF1 is inactivated through mutation in a subset of T-ALL cases but elevated LEF1 expression and activating mutations have also been identified in this disease. Here we show, in a murine model of T-ALL arising due to <i>E2a</i> inactivation, that the developmental timing of <i>Lef1</i> mutation impacts its ability to function as a cooperative tumor suppressor or oncogene. T cell transformation in the presence of LEF1 allows leukemic cells to become addicted to its presence. In contrast, deletion prior to transformation both accelerates leukemogenesis and results in leukemic cellsFrontiers in immunologyOncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in <i>E2a^-/-</i> T Acute Lymphoblastic Leukemia.PMC8971981R01 AI079213R21 AI096530R21 AI119894P30 CA014599Xue HHCarr TDias SSigvardsson MLe Beau MMKee BLMcGregor SVerykokakis MBartom ETfalseOncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in <i>E2a^-/-</i> T Acute Lymphoblastic Leukemia.T lymphocyte acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease affecting T cells at multiple stages of their development and is characterized by frequent genomic alterations. The transcription factor LEF1 is inactivated through mutation in a subset of T-ALL cases but elevated LEF1 expression and activating mutations have also been identified in this disease. Here we show, in a murine model of T-ALL arising due to <i>E2a</i> inactivation, that the developmental timing of <i>Lef1</i> mutation impacts its ability to function as a cooperative tumor suppressor or oncogene. T cell transformation in the presence of LEF1 allows leukemic cells to become addicted to its presence. In contrast, deletion prior to transformation both accelerates leukemogenesis and results in leukemic cells2022-01-01T00:00:00Z20222026-04-08T18:06:55.955Z2025-04-05T22:19:38.995ZS-EPMC89719813537105710.3389/fimmu.2022.845488