Integrating Ideas on Insertional Mutagenesis by Gene Transfer Vectors

Abstract

The 3rd Stem Cell Clonality and Genotoxicity Retreat was held 12–13 December 2006, directly following the 48th annual meeting of the American Hematological Society held in Orlando, Florida. This series of retreats was organized by David Williams, Chris Baum, and Christof von Kalle of Cincinnati Children's Hospital. The impetus was the incidence of insertional leukemogenesis arising in the French gene therapy trial treating X-linked severe combined immunodeficiency disease (X-SCID) in 2002. Prior to 2002, the risk of insertional mutagenesis from gene transfer vectors was a theoretical one that had not been followed up with rigorous proactive studies. Of course, this all changed after the adverse events in the French trial and a case of insertional mutagenesis discovered in an animal study earlier the same year by Chris Baum's group. In the following years, evidence was found for clonal dominance in hematopoietic stem cells transduced with retroviral vectors in both mice and macaques, and in patients with chronic granulomatous disease (CGD) treated with gene-corrected hematopoietic cells.