Figure 7.

GSH Depletion Synergizes with Conventional Chemotherapy to Reduce AML Cells In Vivo

(A) Experimental outline combination therapy in chimeric mice generated as depicted in Figure 3A. Lethally irradiated WT recipients were transplanted with 10⁶ iMLL-AF9;CD45.2⁺ BM cells and 10⁶ WT CD45.1⁺ BM cells. After two weeks, leukemia was induced by doxycycline in the food. Upon AML development, mice were treated with AraC-doxorubicin (Chemo) and BSO or vehicle for 10 days before flow cytometry analysis.

(B–F) BM leukemic (MLL-AF9⁺) or WT (B) CD45⁺ cells, (C) hematopoietic-lineage-negative (lin⁻) cells, (D) lin⁻ckit⁺sca1⁻ (LK) cells, (E) lin⁻ckit⁺sca1⁺ (LSK) cells, and (F) LSK CD48⁺ multipotent progenitors (MPP).

(G) GSH measured by mBCI staining in lin-ckit^low (LK^lo) AML cells from mice treated with combined BSO therapy (red) or with standard induction chemotherapy only (black). Each dot represents a mouse. (B–G) Data are mean ± SEM. ^∗p < 0.05; ^∗∗p < 0.01; unpaired two-tailed t test.

(H) Disease-free AML mice treated with combined BSO therapy (red) or with standard induction chemotherapy only (black; n = 6).

(I) Disease-free mice after lethal irradiation and transplantation of BM cells from mice in (H) (n = 4–6). Recipient mice were fed with doxycycline-containing pellets. (H and I) Logrank test.