Figure 2.

Low-dose bafilomycin A1 improves the pathology of mice engrafted with primary human B-acute lymphoblastic leukemia CD34⁺CD19⁺ cells. (A, B) Representative FACS scatter plots showing the proportions (%) of human CD45 cells in the bone marrow (BM) or peripheral blood (PB) from NSG xenografts following in vivo treatment with vehicle or 0.1 mg/kg bafilomycin A1 (n=5/group, ALL#21-23,25-26). (C, D) Flow cytometric analysis of B-cell acute lymphoblastic leukemia (B-ALL) CD34⁺CD19⁺ cells in the BM or PB from NSG mice treated with vehicle or 0.1 mg/kg bafilomycin A1 (n=5/group). (E) In vivo bafilomycin A1 (0.1 mg/kg) treatment after transplantation significantly reduced leukemic burden (n=5/group). (F) Upper panel, photographs of livers recovered from NSG mice engrafted with B-ALL CD34⁺CD19⁺ cells after the indicated days of treatment with bafilomycin A1 (0.1 mg/kg) or vehicle. Lower panel, the liver coefficient (the ratio of the weight of liver to the total body weight). (G) Upper panel, photographs of spleens recovered from NSG mice engrafted with B-ALL CD34⁺CD19⁺ cells after the indicated days of treatment with bafilomycin A1 or vehicle. Lower panel, the spleen coefficient (the ratio of the weight of spleen to the total body weight). (H) Upper panel, hematoxylin and eosin–stained sections from livers of NSG mice engrafted with B-ALL CD34⁺CD19⁺ cells after treatment with vehicle or bafilomycin A1 (0.1 mg/kg). Leukemic infiltration is indicated by arrows. Lower panel, immunohistochemistry of livers stained for cells expressing human CD19; leukemic infiltration is indicated by arrows. (I) Analysis at days 40-90 for the indicated PB cells, as measured by complete blood count. (J) A proposed working model of bafilomycin A1 targeting both B-ALL cells and their leukemia stem cells. Ctrl and C: control; M: model; T: treatment; Baf-A1: bafilomycin A1; WBC, white blood cells; RBC, red blood cells; HGB, hemoglobin; PLT, platelets.