title: LMO2 at 25 years: a paradigm of chromosomal translocation proteins.
abstract: LMO2 was first discovered through proximity to frequently occurring chromosomal translocations in T cell acute lymphoblastic leukaemia (T-ALL). Subsequent studies on its role in tumours and in normal settings have highlighted LMO2 as an archetypical chromosomal translocation oncogene, activated by association with antigen receptor gene loci and a paradigm for translocation gene activation in T-ALL. The normal function of LMO2 in haematopoietic cell fate and angiogenesis suggests it is a master gene regulator exerting a dysfunctional control on differentiation following chromosomal translocations. Its importance in T cell neoplasia has been further emphasized by the recurrent findings of interstitial deletions of chromosome 11 near LMO2 and of LMO2 as a target of retroviral insertion gene activation during gene therapy trials for X chromosome-linked severe combined immuno-deficiency syndrome, both types of event leading to similar T cell leukaemia. The discovery of LMO2 in some B cell neoplasias and in some epithelial cancers suggests a more ubiquitous function as an oncogenic protein, and that the current development of novel inhibitors will be of great value in future cancer treatment. Further, the role of LMO2 in angiogenesis and in haematopoietic stem cells (HSCs) bodes well for targeting LMO2 in angiogenic disorders and in generating autologous induced HSCs for application in various clinical indications.
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chambers
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK terence.rabbitts@imm.ox.ac.uk.
authors.forename: Terence H
authors.initials: TH
authors.lastname: Rabbitts
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D011518:Proto-Oncogene Proteins
keywords: LMO2; X chromosome-linked severe combined immuno-deficiency syndrome; angiogenesis; chromosomal translocations; haematopoiesis; leukaemia