LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1

Science. 2003 Oct 17;302(5644):415-9. doi: 10.1126/science.1088547.


We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Clinical Trials as Topic
  • Clone Cells / physiology
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation
  • Gene Transfer Techniques
  • Genetic Therapy / adverse effects*
  • Genetic Vectors*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Infant
  • LIM Domain Proteins
  • Leukemia-Lymphoma, Adult T-Cell / etiology*
  • Metalloproteins / genetics*
  • Mutagenesis, Insertional
  • Promoter Regions, Genetic
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Proto-Oncogenes
  • Receptors, Interleukin-2 / genetics
  • Retroviridae / genetics*
  • Retroviridae / physiology
  • Severe Combined Immunodeficiency / therapy*
  • T-Lymphocytes / physiology*
  • Transcription, Genetic
  • Virus Integration
  • Virus Replication


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • LIM Domain Proteins
  • LMO2 protein, human
  • MAS1 protein, human
  • Metalloproteins
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptors, Interleukin-2