In vivo protection of hematopoietic cells from alkylator-mediated DNA damage.
Strategies that confer chemoresistance to hematopoietic stem and progenitor cells have two important future applications in the treatment of cancer and genetic diseases. Because dose-intensification of many cancer chemotherapy protocols is limited by severe hematopoietic toxicities, generation of primitive hematopoietic cells resistant to DNA damage mediated by chemotherapy may protect patients from life-threatening blood cytopenias. In addition, in the context of genetic diseases, overexpression of a chemoresistance gene in stem and progenitor cells may allow for the enrichment of small numbers of transduced cells that would not possess an in vivo selective advantage. In this report, I discuss studies that use the DNA repair protein O6-methylguanine DNA methyltransferase to protect hematopoietic cells from alkylator therapy. I focus on investigations evaluating the ability of O6-methylguanine-DNA methyltransferase mutant proteins to confer heightened resistance to alkylator-mediated DNA damage in vivo.
Pollok
Karen E
KE
Herman B Wells Center for Pediatric Research, The Riley Hospital for Children, 1044 West Walnut Street R4 427, Indianapolis, IN 46202, USA. kpollok@iupui.edu
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair; D004351:Drug Resistance; D005786:Gene Expression Regulation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics
D018906:Antineoplastic Agents, Alkylating; D019853:O(6)-Methylguanine-DNA Methyltransferase