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CDK9 as a potential molecular target in NK cell leukemia/lymphoma
Effect of BAY 1143572 on CDK9 activity in NK-cell leukemia/lymphoma lines
BAY 1143572 had very little effect on the total amount of RNAPII protein in any of the cell lines tested but inhib- ited phosphorylation of RNAPII CTD at the Ser2 site in a dose-dependent manner. In contrast, phosphorylation of RNAPII at the Ser5 site was not affected by this agent in any of the lines. BAY 1143572 treatment did decrease c- Myc and Mcl-1 protein levels in a dose-dependent manner in all of the lines (Figure 2).
BAY 1143572 inhibits growth of primary ANKL cells isolated from patients
IC50 values for BAY 1143572 after 24 hours of incuba- tion with CD56-positive cells isolated from five healthy volunteers were 0.65, 0.56, and 0.27–1.34 mM, (mean, median, and range, respectively). Cell viability curves for BAY 1143572 showed an initial decrease at concentrations up to around 1.0 uM, almost reaching a plateau at around 100.0 uM. Thus, some of the CD56-positive cells isolated from healthy volunteers remained viable even after expo-
AB
Figure 1. BAY 1143572 inhibits proliferation and induces apoptosis in natural killer (NK) cell leukemia/lymphoma lines. (A) Viability of NK-cell leukemia/lymphoma lines on exposure to different concentrations of BAY 1143572 for 72 hours. The IC50 value is shown for each line. IC50 was defined as the concentration of an inhibitor that reduced cell survival to 50% of the untreated control value, with the highest viability (no inhibitor) defined as 100%, and the lowest viability defined as 0%. Each graph shows one representative result of three independent experiments. (B) NK-cell leukemia/lymphoma lines were treated with different concentrations of BAY 1143572 for 72 hours followed by assessing apoptosis via Annexin V and propidium iodide (PI; nuclear) staining. BAY 1143572 concentrations are indicated above the panels, and the percentage of cells in each quadrant is given. Each graph shows one representative result of three independent experiments.
haematologica | 2018; 103(12)
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