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.
|Original language||English (US)|
|Number of pages||7|
|Journal||Current hematology reports|
|State||Published - Jul 2003|
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