Role of MicroRNAs From Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma

Abstract

microRNAs (miRNAs) are increasingly recognized as significant players in oncogenesis and tumor biology through post-transcriptional gene regulation impacting broad pathways of proliferation, differentiation, apoptosis, metastasis, and cell survival. Recent studies have found abnormal expression of miRNAs in multiple myeloma (MM). Currently, the precise role of these miRNAs in the biology of MM remains to be elucidated, although they are predicted to be involved in plasma cell proliferation, survival, homing, or in MM cell interactions with the bone marrow microenvironment. Furthermore, a limited number of studies focusing on MM precursor disease (monoclonal gammopathy of undetermined significance [MGUS]) reveal significant differences in miRNA profiles between MGUS and normal plasma cells. Interestingly, several of the microRNAs differentially expressed in MGUS also show aberrant expression in MM, suggesting a role in early myelomagenesis. miRNA profiles can discriminate molecular subtypes of MM that are defined based on gene expression profiling (GEP) and cytogenetic abnormalities, demonstrating the potential diagnostic/prognostic utility of miRNA profiling for subclassification of MM. Given the relative stability of miRNA and ability to isolate miRNA from routine clinical specimens, miRNA analysis promises to facilitate personalized diagnostics and therapies, and to provide insights into the biology of early myelomagenesis.