Genomics in multiple myeloma: Biology and clinical implications

The advent of new techniques, such as interphase fluorescence in situ hybridization, and, more recently, global array-based gene expression profiling, has accelerated genomic research in myeloma. Distinct biologic subtypes, characterized by unique genetic abnormalities with differing clinical outcomes, have been identified. The identification of these primary genetic defects, and the deregulated oncogenes and pathways in myeloma, has allowed for the development of more targeted therapies. This has led to the discovery of an increased number of active agents in the treatment of myeloma. Genetics also have prognostic importance in myeloma. Recent studies have elucidated a genetic prognostic hierarchy, and have enabled improved definition of the prognostic significance of their interactions. The current challenges are to: improve the dissection of the genetic heterogeneity of the disease; better define progression events; improve the risk stratification of patients; more accurately select patients who will respond well to a particular treatment; and develop more rational combinations of treatment. Genomics will have an important role to play in all of these goals.