Gene therapy: therapeutic gene causing lymphoma

Nature. 2006 Apr 27;440(7088):1123. doi: 10.1038/4401123a.


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.

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Clinical Trials as Topic / adverse effects
  • Clinical Trials as Topic / methods
  • Disease Models, Animal*
  • Dogs
  • Genetic Therapy / adverse effects*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Lymphoma, T-Cell / etiology
  • Lymphoma, T-Cell / genetics*
  • Mice
  • Mice, SCID
  • Oncogenes / genetics*
  • Receptors, Interleukin-2 / genetics*
  • Severe Combined Immunodeficiency / genetics*
  • Severe Combined Immunodeficiency / therapy*
  • Time Factors


  • Receptors, Interleukin-2