Lethal giant larvae 1 tumour suppressor activity is not conserved in models of mammalian T and B cell leukaemia.
In epithelial and stem cells, lethal giant larvae (Lgl) is a potent tumour suppressor, a regulator of Notch signalling, and a mediator of cell fate via asymmetric cell division. Recent evidence suggests that the function of Lgl is conserved in mammalian haematopoietic stem cells and implies a contribution to haematological malignancies. To date, direct measurement of the effect of Lgl expression on malignancies of the haematopoietic lineage has not been tested. In Lgl1⁻/⁻ mice, we analysed the development of haematopoietic malignancies either alone, or in the presence of common oncogenic lesions. We show that in the absence of Lgl1, production of mature white blood cell lineages and long-term survival of mice are not affected. Additionally, loss of Lgl1 does not alter leukaemia driven by constitutive Notch, c-Myc or Jak2 signalling. These results suggest that the role of Lgl1 in the haematopoietic lineage might be restricted to specific co-operating mutations and a limited number of cellular contexts.
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
Edwin D
ED
Hawkins
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
Jane
J
Oliaro
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
Kelly M
KM
Ramsbottom
Stem Cell Research Group, Australian Centre for Blood Diseases, Monash University and Alfred Health, Melbourne, Victoria, Australia.
Stephen B
SB
Ting
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
Faruk
F
Sacirbegovic
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
Michael
M
Harvey
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia ; Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Tanja
T
Kinwell
Institut Curie, Centre Universitaire, Bat 110 91405, Orsay, France ; Centre National de la Recherche Scientifique UMR 3306, Orsay, France ; INSERM (Institut National de la Santé et de la Recherche Médicale) U1005, Orsay, France.
Jacques
J
Ghysdael
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
Ricky W
RW
Johnstone
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia ; Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Patrick O
PO
Humbert
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia ; Centre for Micro-Photonics, Swinburne University of Technology, Hawthorn, Victoria, Australia.
Sarah M
SM
Russell
D000818:Animals; D016026:Bone Marrow Transplantation; D019070:Cell Lineage / Q000502:physiology; D003598:Cytoskeletal Proteins; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D015448:Leukemia, B-Cell / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D017931:DNA Primers; D018398:Homeodomain Proteins; C082939:Llgl1 protein, mouse; D025521:Tumor Suppressor Proteins