Catálogo de publicaciones - revistas

<jats:p> Transposable elements of the <jats:italic>mariner</jats:italic> /Tc1 family are postulated to have spread by horizontal transfer and be relatively independent of host-specific factors. This was tested by introducing the <jats:italic>Drosophila mauritiana</jats:italic> element <jats:italic>mariner</jats:italic> into the human parasite <jats:italic>Leishmania major</jats:italic> , a trypanosomatid protozoan belonging to one of the most ancient eukaryotic lineages. Transposition in <jats:italic>Leishmania</jats:italic> was efficient, occurring in more than 20 percent of random transfectants, and proceeded by the same mechanism as in <jats:italic>Drosophila</jats:italic> . Insertional inactivation of a specific gene was obtained, and a modified <jats:italic>mariner</jats:italic> element was used to select for gene fusions, establishing <jats:italic>mariner</jats:italic> as a powerful genetic tool for <jats:italic>Leishmania</jats:italic> and other organisms. These experiments demonstrate the evolutionary range of <jats:italic>mariner</jats:italic> transposition in vivo and underscore the ability of this ubiquitous DNA to parasitize the eukaryotic genome. </jats:p>

<jats:p>In allogeneic bone marrow transplantation (allo-BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia (GvL) and immune reconstitution. However, their use is limited by the risk of severe graft-versus-host disease (GvHD). Eight patients who relapsed or developed Epstein-Barr virus–induced lymphoma after T cell–depleted BMT were then treated with donor lymphocytes transduced with the herpes simplex virus thymidine kinase (HSV-TK) suicide gene. The transduced lymphocytes survived for up to 12 months, resulting in antitumor activity in five patients. Three patients developed GvHD, which could be effectively controlled by ganciclovir-induced elimination of the transduced cells. These data show that genetic manipulation of donor lymphocytes may increase the efficacy and safety of allo-BMT and expand its application to a larger number of patients.</jats:p>