Figure 6
Figure 6. Pharmacodynamic analyses after selumetinib dosing in vivo shows prolonged inhibition of p-ERK and induction of apoptosis. Western analyses of spleen cells from mice engrafted with Ras pathway mutant ALL cells after 72 hours of 100 mg/kg (A, L897, KRAS) or 25 mg/kg BID (B, L779, NRAS). Flow cytometric analyses of the spleen harvests from L897 primagrafts stained with antibodies to mouse CD45, human CD19, CD10, and CD34, along with annexin V. Dot plot showing CD10 and CD19 expression of cells gated as lymphoid by light scatter and then for mouse CD45 negativity (C). CD10+CD19+ cells are then gated and displayed as histograms showing annexin-V fluorescence (D).

Pharmacodynamic analyses after selumetinib dosing in vivo shows prolonged inhibition of p-ERK and induction of apoptosis. Western analyses of spleen cells from mice engrafted with Ras pathway mutant ALL cells after 72 hours of 100 mg/kg (A, L897, KRAS) or 25 mg/kg BID (B, L779, NRAS). Flow cytometric analyses of the spleen harvests from L897 primagrafts stained with antibodies to mouse CD45, human CD19, CD10, and CD34, along with annexin V. Dot plot showing CD10 and CD19 expression of cells gated as lymphoid by light scatter and then for mouse CD45 negativity (C). CD10+CD19+ cells are then gated and displayed as histograms showing annexin-V fluorescence (D).

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