Figure 3
Figure 3. Longitudinal analysis of the relative abundance of gene-corrected cell clones. (A-G) The proportion of cells containing each integration site is shown on the y-axis; time after gene therapy in months (m) is on the x-axis. The proportion was calculated from the sequence counts as described in supplemental Reports 2, 3, and 4. The gene names for the most abundant clones are shown within each panel. “NR” indicates near the gene, “IN,” within the gene. The adverse events in the trial were as follows, designated by patient (p) number, genes involved, and time of event: p4, LMO2, 30m; p5, LMO2, 20m; p7, CCND2, 68m; p10, LMO2 and BMI1/SPAG6, 33m. (H) Comparison of unique integration site sequences at early versus late time points. Pairs of time points were chosen so that similar sets of restriction enzymes were used for analysis, because recovery using a greater number of restriction enzymes results in recovering a greater number of sites. Thus for some of the patients the last time point was not used in favor of earlier time points with more data. Restriction enzymes used were ApoI, AvrII/NheI/SpeI, BstYI, MseI, NlaIII, and Tsp509I (patients no. 1, no. 2, no. 6, and no. 8); ApoI, AvrII/NheI/SpeI, BstYI, and MseI (patient no. 10); and AvrII/NheI/SpeI and MseI (patients no. 5 and no. 7).

Longitudinal analysis of the relative abundance of gene-corrected cell clones. (A-G) The proportion of cells containing each integration site is shown on the y-axis; time after gene therapy in months (m) is on the x-axis. The proportion was calculated from the sequence counts as described in supplemental Reports 2, 3, and 4. The gene names for the most abundant clones are shown within each panel. “NR” indicates near the gene, “IN,” within the gene. The adverse events in the trial were as follows, designated by patient (p) number, genes involved, and time of event: p4, LMO2, 30m; p5, LMO2, 20m; p7, CCND2, 68m; p10, LMO2 and BMI1/SPAG6, 33m. (H) Comparison of unique integration site sequences at early versus late time points. Pairs of time points were chosen so that similar sets of restriction enzymes were used for analysis, because recovery using a greater number of restriction enzymes results in recovering a greater number of sites. Thus for some of the patients the last time point was not used in favor of earlier time points with more data. Restriction enzymes used were ApoI, AvrII/NheI/SpeI, BstYI, MseI, NlaIII, and Tsp509I (patients no. 1, no. 2, no. 6, and no. 8); ApoI, AvrII/NheI/SpeI, BstYI, and MseI (patient no. 10); and AvrII/NheI/SpeI and MseI (patients no. 5 and no. 7).

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