Related Experiment Video
Updated: Apr 18, 2026
Author Spotlight: Identification and Isolation of Quiescent Leukemia Stem Cells from Zebrafish T-ALL
Published on: July 19, 2024
ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7
Steven Goossens1, Enrico Radaelli2, Odile Blanchet3
11] Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [2] Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium [3] Unit for Molecular and Cellular Oncology, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [4] Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.
Abstract:
Early T-cell precursor leukaemia (ETP-ALL) is a high-risk subtype of human leukaemia that is poorly understood at the molecular level. Here we report translocations targeting the zinc finger E-box-binding transcription factor ZEB2 as a recurrent genetic lesion in immature/ETP-ALL. Using a conditional gain-of-function mouse model, we demonstrate that sustained Zeb2 expression initiates T-cell leukaemia. Moreover, Zeb2-driven mouse leukaemia exhibit some features of the human immature/ETP-ALL gene expression signature, as well as an enhanced leukaemia-initiation potential and activated Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signalling through transcriptional activation of IL7R. This study reveals ZEB2 as an oncogene in the biology of immature/ETP-ALL and paves the way towards pre-clinical studies of novel compounds for the treatment of this aggressive subtype of human T-ALL using our Zeb2-driven mouse model.
