Journal article
The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal
MP McCormack, LF Young, S Vasudevan, CA De Graaf, R Codrington, TH Rabbitts, SM Jane, DJ Curtis
Science | Published : 2010
Abstract
The LMO2 oncogene causes a subset of human T cell acute lymphoblastic leukemias (T-ALL), including four cases that arose as adverse events in gene therapy trials. To investigate the cellular origin of LMO2-induced leukemia, we used cell fate mapping to study mice in which the Lmo2 gene was constitutively expressed in the thymus. Lmo2 induced self-renewal of committed T cells in the mice more than 8 months before the development of overt T-ALL. These self-renewing cells retained the capacity for T cell differentiation but expressed several genes typical of hematopoietic stem cells (HSCs), suggesting that Lmo2 might reactivate an HSC-specific transcriptional program. Forced expression of one s..
View full abstractGrants
Awarded by Medical Research Council
Funding Acknowledgements
We thank C. Talora and I. Screpanti for Lck-Notch3-IC transgenic mice; D. Izon for the MIG-Hhex retroviral vector; A. Strasser for comments on the manuscript; G. Smyth for advice on bioinformatics; and L. Ta, R. Bowyer, L. Mizhiritzky, and J. Davis for animal husbandry. This work was supported by grants (to M. P. M., S. M. J., and D. J. C.) from the Cancer Council of Victoria and National Health and Medical Research Council of Australia (NHMRC) (project grant 382901); a grant-in-aid (to M. P. M. and D.J.C.) from the Leukaemia Foundation; and grants (to T. H. R.) from the Medical Research Council UK (programme grant G0600914) and Leukaemia Research UK (programme grant 07036). D.J.C. is an R. D. Wright Biomedical Research Fellow, and S.M.J. is a Principal Research Fellow of the NHMRC.