1. Volume 20, Issue 8, Pages 1485-1487 (August 2012)
Chemoprotection in Brain Tumor Patients: Another Success for Stem Cell Gene Therapy 
Brian P Sorrentino 
Molecular Therapy 
Volume 20, Issue 8, Pages (August 2012)
DOI: /mt
Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

2. Figure 1
Tumor sensitization with O6-benzylguanine, accompanied by gene therapy–mediated hematopoietic protection. (a) The events occurring in a brain tumor cell expressing wild-type MGMT (WT MGMT, green shapes) when treated with O6-benzylguanine (6BG, blue squares) and temozolomide (TMZ). Methyl adducts (M, purple triangles) added to DNA by TMZ can be removed and repaired by MGMT in the absence of 6BG. When 6BG is present, it binds to and depletes MGMT, thereby sensitizing the tumor cell to TMZ-induced DNA damage, leading to apoptosis. 6BG can thus overcome tumor cell resistance due to MGMT expression. (b) A mutated P140K MGMT gene (teal shape) can be introduced into normal hematopoietic stem cells (HSCs) via retroviral gene transfer so as to preserve hematopoiesis during drug therapy. This mutation dramatically decreases 6BG binding to P140K MGMT and allows efficient repair of the DNA methyl adducts in the face of 6BG treatment, thereby protecting HSCs and their progeny from this cytotoxic drug combination. This strategy allows host protection in the face of tumor cell sensitization. MGMT, O6-methylguanine methyltransferase.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions