Genetic and Epigenetic Mechanisms in Multiple Myeloma

Abstract

Multiple myeloma (MM) is a malignant disorder due to clonal proliferation of plasma cells in the bone marrow in association with elevated serum or urine monoclonal paraprotein levels. MM is associated, particularly in the most advanced stages of the disease, with severe complication, like lytic bone lesion, anemia, immunodeficiency and renal failure. Despite advances in the understanding of the disease and the use of high-dose chemotherapy, MM remains an incurable disease.

From a genetic standpoint, MM development is a multistep process characterized by the presence of a series of chromosomal abnormalities and complex translocations, involving known oncogenes and tumor-suppressor genes. Genomic aberrations are present with increasing frequency as disease progresses. There is an increasing evidence that, in addition to genomic abnormalities, epigenetic dysregulation plays a pivotal role in MM development, making the picture even more complex.

Keywords: Translocations, hyperdiploidy, non-hyperdiploidy, FGFR3, MMSET, MAF, minimal common regions, myc, ras, TP53, NFB, IRF4, epigenetics, histones, microRNAs.