In vivo response to PR-104 in an AKR1C3-overexpressing BCP-ALL xenograft. AKR1C3 cDNA was transduced into ALL-11 (BCP-ALL) resulting in higher levels of AKR1C3 protein expression, comparable to levels observed in T-ALL xenografts (A). These cells were then engrafted into NSG mice, and when the proportion of hCD45 cells in the PB reached 1%, mice were treated with PR-104 at 200 mg/kg for 2 weeks. (B) Kaplan-Meier plot shows the event-free survival of mice treated with PR-104 (solid lines) and engrafted with either the AKR1C3 cDNA (blue), the empty vector (orange), or the untransduced xenograft (green). PR-104 treatment significantly increased survival of AKR1C3 overexpressing mice compared with empty vector (Mantel-Cox analysis, P < .0001) Vehicle-treated mice appear in the broken lines. (C) Engraftment was monitored by the proportion of hCD45 cells in the PB of each mouse, and an event was recorded when it reached 25%.