(A) Scheme of experimental strategy showing transplant with LIC-enriched AML cells, treatment groups (n = 4 recipient mice per group), and flow analysis. (B) Kaplan-Meier survival curve of partially conditioned C57BL/6 mice (CD45.2⁺) transplanted with 10,000 c-Kit⁺CD45.1⁺ CD45.2⁺ MLL-AF9 leukemic splenocytes (n = 4 mice per group). Four days later, 6-week osmotic pumps containing A21+A196b or CA21+CA196b (shaded area denotes time of pump activity) were implanted in the mice, and mice were followed for survival. Insets show flow plots of MLL-AF9 c-Kit⁺CD45.1⁺CD45.2⁺ cells in mice at the indicated time points. (C) TaqMan analysis quantifies the steady state level of mature miR-21 and miR-196b in the peripheral white blood cells of WT mice 10 days after implantation of pumps with the indicated antagomirs. (D and F) MOE is effective in vitro, but ineffective in vivo, at antagonizing microRNA in the MLL-AF9 mouse model of AML. (D) Enumeration of CFU replating after control or MOE (21+196b) treatment of MLL-AF9–transformed cells. (n = 3, mean ± SD). (E) Repeat of transplant as in part B using 10,000 c-Kit⁺CD45.1⁺CD45.2⁺ MLL-AF9 leukemic splenocytes but with MOE (n = 3 mice per group). (F) TaqMan analysis quantifies the steady state levels of mature miR-21 and miR-196b in the peripheral white blood cells of WT mice 10 days after implantation of pumps with the indicated MOE. Note that the MOE lack a cholesterol moiety. ***P < 0.001.