Figure 6.
Figure 6. Dasatinib is effective in vivo against ABL-class fusions. (A) Levels of human CD45/CD19+ blasts in the peripheral blood of NSG mice injected with primary B-ALL cells. (B) Spleen weight of NSG mice at harvest. (C) NSG mice were injected with primary leukemic cells. Upon peripheral engraftment of 5% human CD45, animals (n = 5) were treated with vehicle, dasatinib (20 mg/kg per day), dexamethasone (4 mg/mL ad libitum), or dasatinib and dexamethasone combined. Treatment length is indicated by the gray shaded area; animals were euthanized at the last time point. Analysis of slope was measured by linear regression and unpaired 2-way t test comparing vehicle with dasatinib (ALL1, ALL9, ALL13), or 1-way analysis of variance (ANOVA) with Tukey posttest for multiple comparisons (ALL14). (D) Spleen weights were measured at the time of euthanasia. Each point represents the mean ± SD (n = 5). (E) Representative H&E and human CD45 staining of bone marrow and brain harvested from vehicle or dasatinib-treated mice of ALL1. *P < .05, ***P < .001, ****P < .0001. Das, dasatinib; dex, dexamethasone.

Dasatinib is effective in vivo against ABL-class fusions. (A) Levels of human CD45/CD19+ blasts in the peripheral blood of NSG mice injected with primary B-ALL cells. (B) Spleen weight of NSG mice at harvest. (C) NSG mice were injected with primary leukemic cells. Upon peripheral engraftment of 5% human CD45, animals (n = 5) were treated with vehicle, dasatinib (20 mg/kg per day), dexamethasone (4 mg/mL ad libitum), or dasatinib and dexamethasone combined. Treatment length is indicated by the gray shaded area; animals were euthanized at the last time point. Analysis of slope was measured by linear regression and unpaired 2-way t test comparing vehicle with dasatinib (ALL1, ALL9, ALL13), or 1-way analysis of variance (ANOVA) with Tukey posttest for multiple comparisons (ALL14). (D) Spleen weights were measured at the time of euthanasia. Each point represents the mean ± SD (n = 5). (E) Representative H&E and human CD45 staining of bone marrow and brain harvested from vehicle or dasatinib-treated mice of ALL1. *P < .05, ***P < .001, ****P < .0001. Das, dasatinib; dex, dexamethasone.

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