By searchingdatasets from the Multiple Myeloma Research Foundation (MMRF) CoMMpass (Clinical Outcomes in MM to Personal Assessment of Genetic Profile) study (n = 766) and Gene Expression Omnibus (accession GSE24080, n = 559), RUNX3, a member of runt-related transcription factor family (referred to as RUNXs), is shown to serve as a potential driver for RRMM or secondary plasma cell leukemia (PCL). This evidence concerns the gene RUNX3 and plasma cell myeloma.