Metabolic Effects of Recurrent Genetic Aberrations in Multiple Myeloma

Simple Summary Cancer is associated with metabolic changes related to increased cell proliferation and growth. These cancer-related metabolic features are largely dictated by specific oncogenes that are activated by chromosomal aberrations and epigenetic alterations in cancer cells. Multiple myeloma is an incurable plasma cell malignancy, which is characterized by recurrent chromosomal aberrations that drive the expression of established oncogenes such as MYC, Cyclin D1, FGFR3/MMSET and MAF/MAFB. In this review, we discuss the specific metabolic features of multiple myeloma plasma cells, and focus on the metabolic consequences of recurrent chromosomal aberrations, thereby providing an outline for the metabolic alterations that characterize multiple myeloma. Oncogene activation and malignant transformation exerts energetic, biosynthetic and redox demands on cancer cells due to increased proliferation, cell growth and tumor microenvironment adaptation. As such, altered metabolism is a hallmark of cancer, which is characterized by the reprogramming of multiple metabolic pathways. Multiple myeloma (MM) is a genetically heterogeneous disease that arises from terminally differentiated B cells. MM is characterized by reciprocal chromosomal translocations that often involve the immunoglobulin loci and a restricted set of partner loci, and complex chromosomal rearrangements that are associated with disease progression. Recurrent chromosomal aberrations in MM result in the aberrant expression of MYC, cyclin D1, FGFR3/MMSET and MAF/MAFB. In recent years, the intricate mechanisms that drive cancer cell metabolism and the many metabolic functions of the aforementioned MM-associated oncogenes have been investigated. Here, we discuss the metabolic consequences of recurrent chromosomal translocations in MM and provide a framework for the identification of metabolic changes that characterize MM cells.