A study published in the Journal of Molecular Diagnostics found that abnormal levels of microRNAs (miRNAs) detected in the bone marrow of patients with multiple myeloma (MM) may also be detectable in peripheral blood, and their measurement may be a way to both mark myeloma onset and track its progression from earlier asymptomatic stages
Several precursor conditions of myeloma have been recognized, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM). Although 1% of individuals with MGUS advance to myeloma each year, this rate is 10% for those with SMM.
"Currently there is no single factor that can predict patients with MGUS or SMM who are likely to progress to myeloma," said lead investigator Katherine R. Calvo, MD, National Institutes of Health (NIH), Bethesda, Maryland. "A biomarker of disease progression in the peripheral blood could assist in the early identification of patients evolving to multiple myeloma."
For the study, the researchers analysed bone marrow, plasma, and serum samples from healthy controls and patients with MM, as well as from patients with MGUS and SMM.
Analysis of fluid from the bone marrow of 20 patients with MM resulted in the identification of 111 miRNAs that showed a 2-fold or greater difference from levels observed in 8 control samples. Approximately 60% of the miRNAs were down-regulated and 38% were up-regulated
Further analysis revealed a unique miRNA signature indicative of myeloma. The bone-marrow signature included 8 members of the let-7 family of miRNAs, each of which showed significant decreases ranging from 6- to 17-fold (P <.03) in patients with MM.
Other experiments determined the miRNA profiles characteristic of myeloma in peripheral blood serum and plasma samples. Using quantitative real-time PCR to measure the miRNA, 18 miRNAs were found to be significantly decreased in bone marrow myeloma samples; of these, 11 (60%) miRNAs were also significantly decreased in serum samples, and 6 of the 11 were also found to be lower in plasma samples (including 3 members of the let-7 miRNA family).
The investigators further explored whether the miRNA pattern of myeloma in precursor diseases changes as the disease progresses. They analysed serum samples in 17 patients with MGUS, 17 with SMM, 13 with MM, and 12 healthy controls. They found that only 4 of the 11 miRNAs (36%) that were reduced in the myeloma serum samples were lower in the MGUS samples.
"This suggests that aberrant expression of these [4] miRNAs may be associated with early events in plasma cell neoplasia," said Dr. Calvo.
Eight of the 11 (73%) miRNAs were decreased in SMM plasma samples. However, 3 (27%) were significantly reduced only in the myeloma samples, suggesting that down-regulation of this group of miRNAs may be related to later events during evolution from precursor disease to myeloma.
"Our findings suggest that the antiproliferative and proapoptotic miRNAs, such as the let-7 family members, are down-regulated in multiple myelomàs microenvironment," said Dr. Calvo. "These findings suggest that measuring expression of miRNAs associated with myeloma progression in the peripheral blood may hold promise for predicting disease progression in MGUS and SMM."
