LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.
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...We previously reported the occurrence of lymphoproliferative diseases in 2 patients, P4 and P5, in our SCID-X1 gene therapy trial (5)....
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...proliferations in P5, P7, and P10 differed from that of P4, which consisted of more mature T cells (5)....
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...The clinical benefit of gene therapy has been tempered by the occurrence of leukemia in 4 SCID-X1 patients in our previously reported trial (5)....
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...A relapse occurred 6 months later, initially characterized by the growth of nonblastic T cells carrying the same Vγ9δ1 TCR and by the same integration site in the LMO2 locus as initially detected (5)....
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...In P4 and P5, the 2 patients with previously characterized adverse events, blast cells harbored a predominant integration site near the transcription start site of the LMO2 gene (Figure 3B), and expression analysis showed that LMO2 transcription increased (5)....
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