Stefan Stein, Marion G Ott, Stephan Schultze-Strasser, Anna Jauch, Barbara Burwinkel, Andrea Kinner, Manfred Schmidt, Alwin Krämer, Joachim Schwäble, Hanno Glimm, Ulrike Koehl, Carolin Preiss, Claudia Ball, Hans Martin, Gudrun Göhring, Kerstin Schwarzwaelder, Wolf-Karsten Hofmann, Kadin Karakaya, Sandrine Tchatchou, Rongxi Yang, Petra Reinecke, Klaus Kühlcke, Brigitte Schlegelberger, Adrian J Thrasher, Dieter Hoelzer, Reinhard Seger, Christof von Kalle, Manuel Grez
Gene-modified autologous hematopoietic stem cells (HSC) can provide ample clinical benefits to subjects suffering from X-linked chronic granulomatous disease (X-CGD), a rare inherited immunodeficiency characterized by recurrent, often life-threatening bacterial and fungal infections. Here we report on the molecular and cellular events observed in two young adults with X-CGD treated by gene therapy in 2004. After the initial resolution of bacterial and fungal infections, both subjects showed silencing of transgene expression due to methylation of the viral promoter, and myelodysplasia with monosomy 7 as a result of insertional activation of ecotropic viral integration site 1 (EVI1)...
February 2010: Nature Medicine