Levels of specific microRNAs (miRNAs) detected in the peripheral blood of patients with monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma may prove to predict progression to multiple myeloma, according to Weixin Wang of the Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, Md., and colleagues (J Mol Diagn. 2015;17:669-78).
The research team analyzed bone marrow aspirates from 20 patients with multiple myeloma and 8 healthy controls and found 11 miRNAs with significantly lower expression. Serum was then analyzed in 17 patients with MGUS, 17 with smoldering multiple myeloma, 13 with multiple myeloma, and 12 healthy controls. Four of 11 miRNAs (let-7i, miR-15a, miR-16, and miR-106b) were significantly decreased in MGUS, suggesting that aberrant expression of these miRNAs may be associated with early neoplastic events. Eight of 11 miRNAs (let-7a, let-7b, let-7i, miR-15a, miR-15b, miR-16, miR-106b, and miR-20a) were decreased in smoldering disease. The other three miRNAs (miR-21, miR-223, and miR-361) were significantly decreased in multiple myeloma but not in MGUS/SMM, suggesting that down-regulation of this group of miRNAs may be related to later events in disease progression, including malignant transformation from precursor disease to myeloma, the researchers wrote.
Small, noncoding miRNA molecules function in posttranscriptional gene regulation through RNA silencing, and many of the gene targets of the 11 miRNAs encode proteins that regulate cell proliferation.
Previous studies have shown that the let-7 family of miRNAs are expressed at low levels in human cancer and stem cells, and these miRNAs were implicated in the current study as well. Let-7 miRNAs silence many genes involved in oncogenesis, cell cycle, proliferation, and apoptosis, including MYC. The researchers found that let-7a and let-7b expression was normal in MGUS and decreased in smoldering disease and multiple myeloma, which may be related to increased MYC expression in disease progression.
Dr. Wang and coauthors reported having no disclosures.