Figure 1.
AML cells with -7/-7q are sensitive to the inhibition of NAMPT. (A) Schematic diagram illustrating the distinct relationships of dose-response curves and drug sensitivity scores (DSS) for 2 different assays. In the CTG viability assay, the area over the dose-response curve is transformed into a DSS. Conversely, in the CTxG apoptosis assay, the area under the dose-response curve is used to calculate the DSS. Larger DSS values indicate increased drug sensitivity. (B) Comparison of dose-response to NAMPT inhibitor daporinad in cells from an AML harboring del(7q) with an AML with diploid chromosome 7 (non -7/-7q). Representative AML samples from -7/-7q and non -7/-7q cohorts with median daporinad EC50 are shown. BM MNCs obtained from fresh biopsy samples were incubated with the drug for 72 hours in 5 concentrations, and viability was determined using the CTG assay. (C) Comparison of daporinad sensitivity of BM or PB MNCs from a cohort of patients with AML and healthy individuals. AML with -7/-7q is compared with AML without -7/-7q and healthy individuals. Cell viability was measured using CTG. (D) Sensitivity to daporinad-induced cell death was measured using CTxG. (E) Ex vivo sensitivity to NAMPT inhibitors in viably frozen cells from patients with and without -7/-7q AML. (F) Sensitivity to daporinad in AML cell lines. Cell lines with del(7q) are shown in red and are significantly more sensitive than cell lines without -7/-7q cell lines by the t test (P ∼ .00094). Cells were incubated with daporinad for 72 hours, and viability was measured with CTG. ∗ P < .05; ∗∗ P < .01; ∗∗∗ P < .001; ∗∗∗∗ P < .0001, by Mann-Whitney U test.