Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in E2a-/- T Acute Lymphoblastic Leukemia

Tiffany Carr, Stephanie McGregor, Sheila Dias, Mihalis Verykokakis, Michelle M. Le Beau, Hai Hui Xue, Mikael Sigvardsson, Elizabeth T. Bartom, Barbara L. Kee

Research output: Contribution to journalArticlepeer-review

1 Citation (SciVal)

Abstract

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.

Original languageEnglish
Article number845488
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 2022 Mar

Subject classification (UKÄ)

  • Cancer and Oncology

Keywords

  • E2a
  • Lef1
  • leukemia
  • lymphocyte
  • thymus

Fingerprint

Dive into the research topics of 'Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in E2a-/- T Acute Lymphoblastic Leukemia'. Together they form a unique fingerprint.

Cite this