The Efficacy Of Ck2 Inhibitors Essay - 974 Words

AML xenograft model: For the proposed studies to test the efficacy of CK2 inhibitor in AML, we have transduced the human AML cell line, U937 and human APML cell line, HL60 with a lentiviral vector carrying the luciferase gene. The luciferase-producing U937 and HL60 cells were injected via the tail-vein into NOD.Cg-Rag1 Il2rg/SzJ (NRG) mice. After 3-5 days, engraftment of AML cells was confirmed by bioluminescence imaging documenting one log increase in quantitative signal measured by the IVIS Xenogen reader. Pilot results in two animals demonstrate that both U937 and HL60 luciferase-producing cells successfully established leukemia (Fig 6). Thus, we have demonstrated the feasibility of the proposed experiments by establishing two luciferase tagged AML murine xenografts models in which to assess therapeutic efficacy of CX-4945. Experimental approach: 2.1) Test the therapeutic efficacy of CX-4945 in AML cell line derived murine xenograft model We will use 4-6 weeks old female, NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ (NRG) mice to create AML xenograft models. Ten mice per treatment group will be injected with 2x106 luciferase expressing U937 cells via tail vein. After confirming engraftment by using bioluminescence imaging, treatment with CX4945 will be initiated. Visible signal or one log increase in signal will be used as indication of engraftment. The treatment group will receive CX4945 at 100mg/ kg via oral gavage, five days a week for three weeks and the control group will