Figure 4. 8F4 treatment depletes leukemia-initiating cells in vivo.
(A) Mice with established leukemia UPN1, and UPN7 were treated with 8F4 or control antibody (IgG) as indicated in Figure 2. LSC were defined as Lin−CD34+CD38−. Zebra plots (left panel) show a representative staining of Lin- human cells in mouse BM before and after treatment with 8F4 or IgG, gated on LSC. Numbers show LSC percentage within human Lin- cells. Right panels show LSC percent (mean± SEM) of all live cells (including mouse and human) in bone marrow for each treatment group. (B) Secondary transfer model was used to test the effect of treatment on LSC as measured by leukemia self-renewing capacity. Mice with established leukemia (UPN2) were treated with 8F4 three times per week starting weeks 7. At week 10, residual leukemia in bone marrow from 8F4-treated mice were transplanted into secondary recipient mice. (C) Representative zebra flow cytometry plots of tissues from the transfer recipient mice at week 16 show no detectable leukemia in the bone marrow, spleen and liver of mice that received the AML transplant from 8F4-treated animals, indicating elimination of LSC populations (n=2–4 mice per treatment group).