Figure 2.
Figure 2. Anti-human CD117 antibodies deplete normal and MDS HSCs in vivo. (A) SR-1 depletes normal human UCB-derived HSCs in vivo, as shown by percent depletion from baseline of human myeloid (human CD45+CD13/33+) chimerism on day 8 and 8 weeks after completion of SR-1 treatment; baseline human myeloid chimerism was determined on day 0, prior to treatment. FACS-purified human UCB HSCs (Lin−CD34+CD38−CD90+CD45RA−) were transplanted into sublethally irradiated NSG pups and baseline myeloid chimerism was obtained on day 0 of the second graft administration, which was ∼12 weeks after initial establishment of xenografts. Xenografted mice were treated with 500 μg of SR-1 or control isotype IgG antibody administered IV on day 1, day 3, day 5, and day 7. *P < .001 compared with IgG control at same time point (Student t test) (n = 3, IgG treated; n = 3, SR-1 treated). (B) SR-1 depletes low-risk MDS HSCs in vivo, as shown by percent depletion from baseline of human myeloid (human CD45+CD13/33+) chimerism on day 8 and 8 weeks after completion of SR-1 treatment; baseline human myeloid chimerism was determined on day 0, prior to treatment. FACS-purified low-risk MDS HSCs (Lin−CD34+CD38−CD90+CD45RA−) were transplanted into sublethally irradiated NSG pups and baseline myeloid chimerism was obtained on day 0 of the second graft administration, which was ∼12 weeks after initial establishment of xenografts. Xenografted mice were treated with 500 μg of SR-1 or control isotype IgG antibody administered IV on day 1, day 3, day 5, and day 7. *P < .001 compared with IgG control at same time point (Student t test) (n = 4, IgG treated; n = 4, SR-1 treated). (C) AMG 191 depletes low-risk MDS HSCs in vivo, as shown by human myeloid (human CD45+CD13/33+) chimerism on prior to treatment on day 0 and then at day 21 and 12 weeks after completion of treatment with AMG 191. FACS-purified low-risk MDS HSCs (Lin−CD34+CD38−CD90+CD45RA−) were transplanted into sublethally irradiated NSG pups and baseline myeloid chimerism was obtained on “day 0,” which was ∼12 weeks after initial establishment of xenografts. Xenografted mice were treated with 75 μg of AMG 191 administered IV on day 1. *P < .001 compared with pretreatment day 0 (Student t test; n = 6, AMG 191 treated).

Anti-human CD117 antibodies deplete normal and MDS HSCs in vivo. (A) SR-1 depletes normal human UCB-derived HSCs in vivo, as shown by percent depletion from baseline of human myeloid (human CD45+CD13/33+) chimerism on day 8 and 8 weeks after completion of SR-1 treatment; baseline human myeloid chimerism was determined on day 0, prior to treatment. FACS-purified human UCB HSCs (Lin−CD34+CD38−CD90+CD45RA−) were transplanted into sublethally irradiated NSG pups and baseline myeloid chimerism was obtained on day 0 of the second graft administration, which was ∼12 weeks after initial establishment of xenografts. Xenografted mice were treated with 500 μg of SR-1 or control isotype IgG antibody administered IV on day 1, day 3, day 5, and day 7. *P < .001 compared with IgG control at same time point (Student t test) (n = 3, IgG treated; n = 3, SR-1 treated). (B) SR-1 depletes low-risk MDS HSCs in vivo, as shown by percent depletion from baseline of human myeloid (human CD45+CD13/33+) chimerism on day 8 and 8 weeks after completion of SR-1 treatment; baseline human myeloid chimerism was determined on day 0, prior to treatment. FACS-purified low-risk MDS HSCs (Lin−CD34+CD38−CD90+CD45RA−) were transplanted into sublethally irradiated NSG pups and baseline myeloid chimerism was obtained on day 0 of the second graft administration, which was ∼12 weeks after initial establishment of xenografts. Xenografted mice were treated with 500 μg of SR-1 or control isotype IgG antibody administered IV on day 1, day 3, day 5, and day 7. *P < .001 compared with IgG control at same time point (Student t test) (n = 4, IgG treated; n = 4, SR-1 treated). (C) AMG 191 depletes low-risk MDS HSCs in vivo, as shown by human myeloid (human CD45+CD13/33+) chimerism on prior to treatment on day 0 and then at day 21 and 12 weeks after completion of treatment with AMG 191. FACS-purified low-risk MDS HSCs (Lin−CD34+CD38−CD90+CD45RA−) were transplanted into sublethally irradiated NSG pups and baseline myeloid chimerism was obtained on “day 0,” which was ∼12 weeks after initial establishment of xenografts. Xenografted mice were treated with 75 μg of AMG 191 administered IV on day 1. *P < .001 compared with pretreatment day 0 (Student t test; n = 6, AMG 191 treated).

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