Of mice and men: how an oncogene transgresses the limits and predisposes to T cell acute lymphoblastic leukemia.
The gene encoding LIM-only 2 (LMO2), an oncogenic transcription factor, is frequently activated in T cell acute lymphoblastic leukemia (T-ALL), but how LMO2 transforms primary hematopoietic cells to induce T-ALL remains an open question. McCormack et al. now show that, in mice, Lmo2 confers self-renewal potential on normally nonrenewing thymocyte progenitor cells, and this property is maintained over four serial transplantations when the cells are transplanted into irradiated mice that lack thymocytes. These leukemia-initiating cells are resistant to irradiation, indicating the need to develop new therapeutic drugs that specifically target the oncogene itself.
Hoang
Trang
T
Institute for Research in Immunology and Cancer, Departments of Pharmacology, Biochemistry, and Molecular Biology, Faculty of Medicine, University of Montreal, Montréal, QC H3C 3J7, Canada. trang.hoang@umontreal.ca
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D060588:LIM Domain Proteins; D008667:Metalloproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009857:Oncogenes / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; C513188:Lmo2 protein, mouse; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins