Lethal giant larvae 1 tumour suppressor activity is not conserved in models of mammalian T and B cell leukaemia

• Published in: PloS one 2014-01, Vol.9 (1), p.e87376-e87376
• Main Authors: Hawkins, Edwin D, Oliaro, Jane, Ramsbottom, Kelly M, Ting, Stephen B, Sacirbegovic, Faruk, Harvey, Michael, Kinwell, Tanja, Ghysdael, Jacques, Johnstone, Ricky W, Humbert, Patrick O, Russell, Sarah M
• Format: Article
• Language: English
• Subjects: Animal models; Animals; B cells; Biology; Bone marrow; Bone Marrow Transplantation; c-Myc protein; Cancer; Cell cycle; Cell division; Cell fate; Cell Lineage - physiology; Cell survival; Disease Models, Animal; DNA Primers - genetics; Drosophila; Gene expression; Hematology; Hematopoietic stem cells; Hematopoietic Stem Cells - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Immunology; Insects; Janus kinase 2; Kaplan-Meier Estimate; Kinases; Laboratories; Larvae; Lesions; Leukemia; Leukemia, B-Cell - metabolism; Leukemia, T-Cell - metabolism; Leukocytes; Liver transplants; Lymphocytes B; Lymphoma; Mammals; Medicine; Mice; Mice, Knockout; Mutation; Myc protein; Notch protein; Oncology; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Signaling; Stem cell transplantation; Stem cells; Survival; Transplants & implants; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0087376

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.