Fig. 2: Distribution of vector integrations into LMO2 and MECOM genes.

a Genomic view of γRV IS close to LMO2 retrieved from patients that developed serious adverse events as a consequence of vector-driven insertional mutagenesis. γRV IS retrieved from P21_ADA is highlighted by a red box. Chromosome, genomic coordinates and scale are indicated. Black lines refer to the position of the indicated γRV IS, black arrows refer to vector orientation. Patient_ID and disease are also indicated: UK, England and F, French SCID-X1 clinical trial. LMO2 genomic structure is indicated by blue boxes and vertical bars that indicate exons; blue arrow indicates the start site and gene transcription. Gene regulatory regions such as CpG islands, Enhancer and Promoter, and histone methylation marks are indicated by the USCS genomic track. b–e Stacked bar plots showing the abundance of γRV IS (years, x-axis) in PB-CD4 (b), Whole (c), MNC (d) and cell-free DNA (e) samples collected at different time points (TP) post-GT. In each column, each γRV IS is represented by different colors, whose height is proportional with the number of genomes retrieved for that IS over the total (%IS Abundance, y-axis). Ribbons connect γRV IS tracked among consecutive TP. The number of unique IS retrieved from each TP is indicated in blue above the column. f, g Quantification of the relative abundance of the γRV close to LMO2 (f) and MECOM (g) measured overtime by ddPCR. h, i Relative level of expression of LMO2 (h) and MECOM (i) measured in the leukemic clone at the diagnosis. Gene expression levels were normalized to GAPDH expression. BM CD34+, PBMC and CD4+ cells from healthy donors are used as reference. LMO2 expression levels measured in T-cell lymphoma developed in a SCID-X1 patient (P9) consequently to a single γRV insertion located 10 kb upstream of the IS described in this work (Fig. 2a). LMO2 expression showed the highest value in P21 blast cells as compared to primary cells and T-cell lymphoma from P9SCID-X1. From f to i, data are presented as mean values ± SEM of technical replicate values. Source data are provided as a Source Data file.