Fig. 1

Iberdomide activity in pomalidomide-resistant cell lines. a Relative cereblon protein (blue bars; left Y-axis) in the pomalidomide-resistant cell lines as determined by densitometry of the Western blots from Supplemental Fig. 3A, normalized to their individual actin loading control and to their parental sensitive counterparts. Represented as % change relative to parental. Overlaid is the relative % proliferation inhibition of iberdomide (iber – 0.1 μM; green bars) on those individual cell lines as determined by 3H-thymidine incorporation. b Western blot analysis showing the effects of either pomalidomide (1 μM) or iberdomide (0.1 μM) on the degradation kinetics of Aiolos in the parental sensitive KMS12BM and pomalidomide-resistant KMS12BM/PR. Actin is shown as a loading control. c PBMC co-culture experiments where isolated, CD3-stimulated PBMCs were incubated with iberdomide (0.0001–1 μM) for 72 h, and then combined with either the parental MM1.S (CFSE-stained) or pomalidomide-resistant MM1.S/PR (CFSE-stained) cells for the final 4 h. CFSE + cells were gated on and evaluated for apoptosis by flow cytometry using Annexin-V and ToPro3⁺ staining. Bars represent % of viable target cells compared to vehicle control (DMSO). Shown here is the representative of three independent experiments