Importantly, AKR1C3 expression (mRNA, protein or intracellular) provides a predictive biomarker of efficacy, as ACHM-025 was significantly more effective against T-ALL PDXs with high AKR1C3 expression versus those with low AKR1C3 expression (p<0.0001)...ACHM-025 exerted profound in vivo efficacy against T-ALL PDXs and eradicated the disease in 7 aggressive T-ALL PDXs. ACHM-025 was significantly more effective than CPM both as a single agent and when used in combination with Ara-C/6MP. Notably, ACHM-025 in combination with nelarabine was curative when used to treat a chemoresistant T-ALL PDX in vivo. The in vivo efficacy of ACHM-025 directly correlated with AKR1C3 expression levels, providing a predictive biomarker for response.