Cytotoxic effects of anti-myeloma agents Bortezomib and Lenalidomide in multiple myeloma cell lines
Multiple myeloma (MM) is an aggressive, highly heterogeneous cancer of the plasma cells accounting for 2% of all cancer deaths. Currently, MM is incurable and the etiology is poorly understood. To study the heterogeneity of MM at the molecular level, the Multiple Myeloma Research Foundation conducted the CoMMpass longitudinal clinical trial. Using genomic data collected in the CoMMpass study, the Banovich lab identified 7,737 eQTLs (expression quantitative trait loci) and utilizes CRISPRi as a screening to validate their functions in gene expression in MM cell lines. In this project, we studied the effects of two drugs: Bortezomib (BTZ) and Lenalidomide (LEN) on MM cell lines with and without dCas9-KRAB (CRISPRi) or dCas9-VP64 (CRISPRa) prior to the addition of a gRNA. BTZ has a significant cytotoxic effect at 10nM on all the cell lines used and the effect of BTZ on cell viability is similar between cell lines with or without dCas9-KRAB/dCas9-VP64. LEN, however, showed minimal effects after 24 and 48 hours, even at the highest 80uM concentration in all cell lines. Furthermore, it was confirmed the effects of BTZ, but not LEN, on apoptosis and cell death in these cell lines using an Annexin V assay and FACS. This study provides important information for the future study in the Banovich lab, to study the effects of the eQTLs on treatment response in the MM cell lines.
