The impact of CRBN mutations on the cell viability of IMiD-sensitive myeloma cell lines. (A) Growth inhibitory (GI50) cell viability measurements for the MM1.sCRBNKO clone 1 cell lines each one expressing a differently mutated CRBN, CRBNWT, or empty vector (EV) in comparison with parental MM1.s. The color of the title for each graph denotes the effect of each mutation on cell viability, where green is associated with reduction in cell viability comparable with parental MM1.s, red denotes no reduction in cell viability, and orange highlights the mutations whose presence leads to partial reduction in cell viability. Cells were treated with dimethyl sulfoxide (DMSO) or increasing concentrations of Len (maximum concentration 20 μM), Pom (maximum concentration 8 μM), Iber (maximum concentration 2 μM), and Mezi (maximum concentration 1 μM) for 5 days. Cell viability was determined using the CellTiter-Blue assay and expressed as a % of DMSO control. Results are the mean ± standard error of the mean (SEM) of n = 4 biological replicates. (B) Heat map summarizing the results shown in Figure 2A but with the drug concentration expressed as a percentage of the maximum for that cell line, Len 100% = 20 μM, Pom 100% = 8 μM, etc, and cell viability expressed as a percentage of DMSO control.

The impact of CRBN mutations on the cell viability of IMiD-sensitive myeloma cell lines. (A) Growth inhibitory (GI50) cell viability measurements for the MM1.sCRBNKO clone 1 cell lines each one expressing a differently mutated CRBN, CRBNWT, or empty vector (EV) in comparison with parental MM1.s. The color of the title for each graph denotes the effect of each mutation on cell viability, where green is associated with reduction in cell viability comparable with parental MM1.s, red denotes no reduction in cell viability, and orange highlights the mutations whose presence leads to partial reduction in cell viability. Cells were treated with dimethyl sulfoxide (DMSO) or increasing concentrations of Len (maximum concentration 20 μM), Pom (maximum concentration 8 μM), Iber (maximum concentration 2 μM), and Mezi (maximum concentration 1 μM) for 5 days. Cell viability was determined using the CellTiter-Blue assay and expressed as a % of DMSO control. Results are the mean ± standard error of the mean (SEM) of n = 4 biological replicates. (B) Heat map summarizing the results shown in Figure 2A but with the drug concentration expressed as a percentage of the maximum for that cell line, Len 100% = 20 μM, Pom 100% = 8 μM, etc, and cell viability expressed as a percentage of DMSO control.

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