Bone marrow and myeloma cellular communication protects from genotoxicity in a drug-specific manner

Multiple myeloma (MM) is an incurable haematological malignancy with most patients eventually developing ad- vanced, relapsing disease and drug resistance (1,2). This may result from protection by BM mesenchymal cells (BM— MSC) interacting with MM cells. As previously reported, DNA damage was reduced in melphalan-treated MM cells that were co-cultured with BM-MSC (3). However it is un- known if this protection is altruistic and genotoxicity in BM-MSC post-exposure to treatment remains unknown. To investigate, an in vitro model of MM was developed. U266 and HS5/BM-MSC cells, were exposed to a clinical dose of melphalan (32.8 μM) or thalidomide (200 pg/ml) for 1hr, both alone and in co-culture (both treated or one compartment treated, then co-cultured). Genotoxicity was assessed using the in vitro comet and micronucleus assays at 1, 16, 48 and 72 hrs. Cell viability was determined by trypan blue exclusion assay. No DNA damage was de- tected by the comet assay in melphalan exposed BM-MSC at any time point. Untreated U266 showed increasing ap- optosis by the micronucleus assay when co-cultured with previously treated BM-MSC, suggesting a bystander effect. Furthermore, whilst cell viability of BM-MSC decreased, U266 samples at 72hr following exposure to melphalan treated (