title: Gene therapy: therapeutic gene causing lymphoma.
abstract: The development of T-cell leukaemia following the otherwise successful treatment of three patients with X-linked severe combined immune deficiency (X-SCID) in gene-therapy trials using haematopoietic stem cells has led to a re-evaluation of this approach. Using a mouse model for gene therapy of X-SCID, we find that the corrective therapeutic gene IL2RG itself can act as a contributor to the genesis of T-cell lymphomas, with one-third of animals being affected. Gene-therapy trials for X-SCID, which have been based on the assumption that IL2RG is minimally oncogenic, may therefore pose some risk to patients.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Niels-Bjarne
authors.initials: NB
authors.lastname: Woods
authors.forename: Virginie
authors.initials: V
authors.lastname: Bottero
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.forename: Inder M
authors.initials: IM
authors.lastname: Verma
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002986:Clinical Trials as Topic / Q000009:adverse effects / Q000379:methods; D004195:Disease Models, Animal; D004285:Dogs; D015316:Genetic Therapy / Q000009:adverse effects*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D009857:Oncogenes / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000628:therapy*; D013997:Time Factors
chemical_list: D015375:Receptors, Interleukin-2