Figure 6.
TAK-981's antileukemic effects in human xenograft AML mouse models (immune-compromised mice). (A-E) Human AML mouse model was established by injecting MOLM-14 cells labeled with luciferase/green fluorescent protein (GFP) (MOLM-14/luciferase/GFP) into NSG mice through tail vein. After confirming leukemia engraftment by bioluminescence imaging, the mice were divided into 2 groups (10 mice per group) and treatment began on day 5 until day 26: control (no treatment) or TAK-981 (7.5 mg/kg formulated in 20% 2-hydroxypropyl-β-cyclodextrin, IV 3 times a week). Representative mice from each group were subjected to serial bioluminescence images (A) and intensity quantitation on days 5, 12, and 20 after leukemic cell injection (B). (C-D) Three representative mice per group were euthanized on day 20 to compare the leukemic burdens between the groups. Cells from the BM and blood were analyzed using flow cytometry. The proportions of GFP+ cells by flow cytometry to identify leukemic cells were compared between the groups. (E) Western blot was performed with sorted leukemic cells to evaluate SUMOylated proteins in each group. The sample was pooled from individual animals, representing the average levels (supplemental Methods). (F) The overall survival rate in each group (7 mice per group) was estimated by the Kaplan-Meier method. The results are expressed as the mean ± standard error of the mean; ∗P < .05, ∗∗P < .01. CTL, control; SSC, side scatter.

TAK-981's antileukemic effects in human xenograft AML mouse models (immune-compromised mice). (A-E) Human AML mouse model was established by injecting MOLM-14 cells labeled with luciferase/green fluorescent protein (GFP) (MOLM-14/luciferase/GFP) into NSG mice through tail vein. After confirming leukemia engraftment by bioluminescence imaging, the mice were divided into 2 groups (10 mice per group) and treatment began on day 5 until day 26: control (no treatment) or TAK-981 (7.5 mg/kg formulated in 20% 2-hydroxypropyl-β-cyclodextrin, IV 3 times a week). Representative mice from each group were subjected to serial bioluminescence images (A) and intensity quantitation on days 5, 12, and 20 after leukemic cell injection (B). (C-D) Three representative mice per group were euthanized on day 20 to compare the leukemic burdens between the groups. Cells from the BM and blood were analyzed using flow cytometry. The proportions of GFP+ cells by flow cytometry to identify leukemic cells were compared between the groups. (E) Western blot was performed with sorted leukemic cells to evaluate SUMOylated proteins in each group. The sample was pooled from individual animals, representing the average levels (supplemental Methods). (F) The overall survival rate in each group (7 mice per group) was estimated by the Kaplan-Meier method. The results are expressed as the mean ± standard error of the mean; ∗P < .05, ∗∗P < .01. CTL, control; SSC, side scatter.

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