Knockdown of CYP3A4 in BMSCs reduced the stromal-mediated FLT3 TKI resistance of FLT3/ITD AML in the mouse xenograft model. (A) The right panel depicts the mouse xenograft model. Tumors on the left flanks were composed of luciferase-positive (Luc⁺) Molm14 cells and control human primary BMSCs (Control 1° stroma); tumors on the right flanks were composed of Luc⁺ Molm14 cells and human primary BMSCs with shRNA knockdown of CYP3A4 (shCYP3A4 1° stroma). Mice with xenograft tumors were treated with 10 mg/kg sorafenib 3 times per week for 4 weeks. The left panel shows the bioluminescent images representing tumor burden of 5 representative xenograft mice on day 0, day 14, and day 28 after the treatment started. (B) Fold change in the bioluminescent intensity of xenograft tumors with control or shCYP3A4 1° stroma on day 28 relative to day 0 during sorafenib treatment. Data represent the mean ± SEM of 10 independent xenografts. **P < .01. IP, intraperitoneal.