Activation of the T-Cell OncogeneLMO2after Gene Therapy for X-Linked Severe Combined Immunodeficiency

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.