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      LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1

      Science
      American Association for the Advancement of Science (AAAS)

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          Abstract

          We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.

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          Author and article information

          Journal
          Science
          Science
          American Association for the Advancement of Science (AAAS)
          0036-8075
          1095-9203
          October 17 2003
          October 17 2003
          : 302
          : 5644
          : 415-419
          Article
          10.1126/science.1088547
          14564000
          4826f04e-f396-4f8d-9162-11b3749884a2
          © 2003
          History

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