1. AML cells display differential sensitivity to inhibition of IKBKE and TBK1.
AML cells display differential sensitivity to inhibition of IKBKE and TBK1. (A) AML cell lines were infected with lentiviral vectors containing either shRNA targeting luciferase (shLUC) as a negative control, or the indicated IKBKE or TBK1 shRNA. Following selection in puromycin for 3 days, IKBKE and TBK1 protein levels in whole cell lysates were assessed by immunoblotting. Tubulin serves as a loading control. (B) Relative viability of AML cell lines in which IKBKE or TBK1 was depleted by RNA interference was measured 96 hours after puromycin selection. Error bars represent standard error (SE) of at least 2 independent experiments. (C) AML cell lines were infected with lentiviral vectors containing either control shLuc or the indicated IKBKE or TBK1 shRNA. Seventy-two hours later, apoptosis was quantified by annexin V staining and flow cytometry. Error bars represent SE of at least 2 independent experiments. (D) AML cells were infected overnight with lentiviral vectors containing either green fluorescent protein (GFP), kinase dead IKBKE (K38A), or wild-type IKBKE. Relative viable cell number was evaluated 72 hours after infection. Expression of IKBKE was measured by immunoblotting (inset). (E) The indicated AML cell lines were treated with momelotinib or ruxolitinib at the indicated concentrations. Relative viability was measured 72 hours after drug treatment. Error bars represent SE of at least 2 independent experiments. (F) The indicated AML cell lines were treated with momelotinib at the indicated concentration. Relative viability was measured 72 hours after drug treatment. ***P < IC50, 50% inhibitory concentration.
Suhu Liu et al. Blood Adv 2018;2:
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