Figure 1.

CLL cells induced to proliferate are sensitized to MLN4924. (a) CLL cells (N=4) were co-cultured with CD40L-expressing stroma for up to 72 h in the presence or not of 25 ng/ml IL-21 or 1.5 μM CpG-ODN. Cells were collected daily, labeled with 5-ethynyl-2′-deoxyuridine (EdU) and assayed by flow cytometry. Data are mean±S.E. A representative image is shown. (b) CLL cells were co-cultured with CD40L-expressing stroma in the presence or not of 25 ng/ml IL-21. After 72 h, cells were treated with 0.25–1 μM MLN4924 or vehicle control for the indicated time intervals. Apoptosis within the CD19⁺ subset of cells (N=10) was determined by Annexin V and 7-AAD staining. *P<0.05 and **P<0.01 compared with CD40L only