LMO2 -Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1
Centre National de la Recherche Scientifique · Inserm · +15 more institutions
Abstract
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…
Citation impact
- FWCI
- 95.33
- Percentile
- 100%
- References
- 36
Authors
35- SHS. Hacein-Bey-AbinaCorresponding
Centre National de la Recherche Scientifique, Inserm, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Matériaux Ingénierie et Science, Bipar, Laboratoire de Recherche en Informatique
- CVChristof von Kalle
Centre National de la Recherche Scientifique, Inserm, University of Freiburg, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Matériaux Ingénierie et Science, Bipar, Laboratoire de Recherche en Informatique
- MSManfred Schmidt
Centre National de la Recherche Scientifique, Inserm, University of Freiburg, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Matériaux Ingénierie et Science, Bipar, Laboratoire de Recherche en Informatique
- MPMatthew P. McCormack
Centre National de la Recherche Scientifique, Inserm, MRC Laboratory of Molecular Biology, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Matériaux Ingénierie et Science, Bipar, Laboratoire de Recherche en Informatique, Medical Research Council
- NMN. M. Wulffraat
Centre National de la Recherche Scientifique, Inserm, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Matériaux Ingénierie et Science, Bipar, Laboratoire de Recherche en Informatique
Topics & keywords
- Genetic enhancement
- Gene
- Biology
- Cell growth
- Genetics
- Molecular biology
- Cancer research
- Immunology
- Good health and well-being