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- Title
LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.
- Authors
Hacein-Bey-Abina, S; Von Kalle, C; Schmidt, M; McCormack, M P; Wulffraat, N; Leboulch, P; Lim, A; Osborne, C S; Pawliuk, R; Morillon, E; Sorensen, R; Forster, A; Fraser, P; Cohen, J I; de Saint Basile, G; Alexander, I; Wintergerst, U; Frebourg, T; Aurias, A; Stoppa-Lyonnet, D; Romana, S; Radford-Weiss, I; Gross, F; Valensi, F; Delabesse, E; Macintyre, E; Sigaux, F; Soulier, J; Leiva, L E; Wissler, M; Prinz, C; Rabbitts, T H; Le Deist, F; Fischer, A; Cavazzana-Calvo, M
- 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 unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.
- Publication
Science (New York, N.Y.), 2003, Vol 302, Issue 5644, p415
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1088547