Figure 1
From: Ponatinib sensitizes myeloma cells to MEK inhibition in the high-risk VQ model
Re-purposing screen identifies de novo resistance of VQ MM cells to venetoclax. (A) Scheme of drug screening procedure against VQ myeloma cells. (B) AOD IX screening results for compounds at 100 nM and 1000 nM concentration alone or in the presence of 10 nM Trametinib. Results are plotted as Log2 fold change in viability relative to DMSO-treated control wells as measured by CellTiter-Glo Luminescent Assay after 48 h of treatment. Notable compounds are highlighted-see accompanying table in (C). (C) Table detailing selected positive, false negative, and true negative hits from the AOD IX library as highlighted in (B). (D) VQ 4935 and 4938 cells were treated with the indicated concentration of venetoclax for 48 h. Relative viability to DMSO treated control was then measured using the CellTiter-Glo assay. IC50 values were calculated by logistic regression using the GraphPad Prism software. (E) Transcript levels of anti-apoptotic genes Bcl2 and Mcl1 in CD138+ B220- cells from control bone marrow (BM) or VQ recipient BM. FPKM, Fragments Per Kilobase of transcript per Million mapped reads. (F) Ratios of Bcl2:Bcl2l1 and Bcl2:Mcl1 gene expression levels. Results are presented as mean + SD. *p < 0.05.
