Chemogenomics Mapping of Potential Drugs and Targets for Treatment of Multiple Myeloma

Abstract Multiple myeloma (MM) is the second common hematological malignancy affecting about 352,000 worldwide. Some subgroups of MM patients still cannot benefit from the currently available anti-MM drugs and therefore are at high risk of death. The pathological mechanism of MM remains to be unraveled. The identification of a global gene signature for MM might lead toward development of novel diagnostics and therapeutic interventions. Here, we identified common differentially expressed genes (DEGs) shared by 30 MM microarray data sets and compared the common DEGs with those induced by genetic or chemical perturbations. We found some potential therapeutic targets for MM treatment, for example RARA, FGFR1, PML, ROR1, SLAMF7, MTDH and Daxx. as modulating them can reverse the MM-induced gene signature. Based on our analysis results, we also predicted and validated some drug reposition, such as Imatinib, Decitabine, Dexamethasone, Vincristine, Paclitaxel, as well as Bortezomib plus Bafilomycin A1 combination for MM treatment by a literature search, data mining, and in vitro bioassays. This study could provide guidance and indications for the development of MM specific diagnostic biomarkers, indication predictors and therapeutic treatment.