Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in E2a-/- 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 E2a inactivation, that the developmental timing of Lef1 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 cells with altered expression of genes controlling receptor-signaling pathways. Our data demonstrate that the developmental timing of Lef1 mutations impact its apparent oncogenic or tumor suppressive characteristics and demonstrate the utility of mouse models for understanding the cooperation and consequence of mutational order in leukemogenesis.

McGregor, StephanieUniversity of Wisconsin-Madison,Biomedical Sciences Research Center - Alexander Fleming,University of Chicago (författare)
Dias, SheilaUniversity of Chicago (författare)
Verykokakis, MihalisUniversity of Wisconsin-Madison,Biomedical Sciences Research Center - Alexander Fleming (författare)
Le Beau, Michelle M.University of Chicago (författare)
Xue, Hai HuiHackensack University Medical Center (författare)
Sigvardsson, MikaelLund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär lymfopoes,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Molecular Lymphopoiesis,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)stem-msi (författare)
Bartom, Elizabeth T.Northwestern University (författare)
Kee, Barbara L.University of Chicago (författare)
University of ChicagoUniversity of Wisconsin-Madison (creator_code:org_t)

Av författaren/redakt...: Carr, Tiffany; McGregor, Stepha ...; Dias, Sheila; Verykokakis, Mih ...; Le Beau, Michell ...; Xue, Hai Hui; visa fler...; Sigvardsson, Mik ...; Bartom, Elizabet ...; Kee, Barbara L.; visa färre...

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