Activation of the T-Cell Oncogene LMO2 after Gene Therapy for X-Linked Severe Combined Immunodeficiency

MP McCormack, TH Rabbitts - New England Journal of Medicine, 2004 - Mass Medical Soc
MP McCormack, TH Rabbitts
New England Journal of Medicine, 2004Mass Medical Soc
Gene therapy, in which a retrovirus was used to carry the relevant gene (IL2R γc) into a
patient's hematopoietic stem cells, was used to treat 10 boys with X-linked severe combined
immunodeficiency (SCID). A syndrome resembling T-cell leukemia developed in two of the
boys. In both boys—and a third in whom leukemia has not developed—the retrovirus
integrated into the same genomic site, the locus of LMO2, which is involved in childhood
lymphocytic leukemia. This article reviews the molecular biology of these events and …
Gene therapy, in which a retrovirus was used to carry the relevant gene (IL2Rγc) into a patient's hematopoietic stem cells, was used to treat 10 boys with X-linked severe combined immunodeficiency (SCID). A syndrome resembling T-cell leukemia developed in two of the boys. In both boys — and a third in whom leukemia has not developed — the retrovirus integrated into the same genomic site, the locus of LMO2, which is involved in childhood lymphocytic leukemia. This article reviews the molecular biology of these events and discusses their implications for the future of gene therapy.
The New England Journal Of Medicine