SarCNU mediates selection of P140K methylguanine-DNA-methyltransferase transduced human CD34+ cells in vitro

The therapeutic combination O6-benzylguanine (BG) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) can be used to select for P140K methylguanine-DNA-methyltransferase (P140K MGMT) transduced hematopoietic progenitors both in vitro and in vivo. SarCNU is a new alkylating agent which has advantages over BCNU. We tested the ability of P140K MGMT transduced human CD34+ cells to resist SarCNU treatment and be selected for in vitro. BG/SarCNU exposure led to an increase in the proportion of transduced cells from 13 to 27%. The IC90 was increased sixfold by P140K MGMT transduction. These results suggest that SarCNU may be a suitable agent for in vivo selection strategies.